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Hwang, Eun-Sil Shelley

Positions:

Professor of Surgery

Surgery, Advanced Oncologic and Gastrointestinal Surgery
School of Medicine

Vice Chair of Research in the Department of Surgery

Surgery
School of Medicine

Professor of Radiology

Radiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1991

M.D. — University of California at Los Angeles

M.P.H. 2006

M.P.H. — University of California at Berkeley

Intern, General Surgery

Kaiser Foundation Hospital

Resident, General Surgery

Cornell University

Fellow, Breast Surgical Oncology

Memorial Sloan Kettering Cancer Center

Senior Reigstrar, General Surgical Oncology

Singapore General Hospital

Assistant Professor In Residence, Surgery

University of California, San Francisco, School of Medicine

Associate Professor In Residence, Surgery

University of California, San Francisco, School of Medicine

Chief, Division Of Breast Surgery Oncology

University of California, San Francisco, School of Medicine

Professor In Residence, Surgery

University of California, San Francisco, School of Medicine

Surgeon In Chief, Ucsf Helen Diller Family Cancer Center

University of California, San Francisco, School of Medicine

News:

Dr. Shelley Hwang: New measure of mastectomy

March 22, 2016 — The New York Times

Study: Chemo unnecessary in many cases of early-stage breast cancer

October 05, 2015 — NPR’s “Here & Now”

Think pink: Lumpectomy vs. mastectomy

October 04, 2013 — Ivanhoe Newswire

Grants:

Building Interdisciplinary Research Careers in Women's Health

Administered By
Obstetrics and Gynecology
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 26, 2002
End Date
July 31, 2022

TBCRC 034 DFCI 15-174

Administered By
Duke Cancer Institute
AwardedBy
Johns Hopkins University
Role
Principal Investigator
Start Date
March 07, 2016
End Date
June 27, 2022

Comparison of Operative to Medical Endocrine Therapy (COMET) for Low Risk DCIS

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
Alliance for Clinical Trials in Oncology Foundation
Role
Principal Investigator
Start Date
June 01, 2016
End Date
December 01, 2021

Translational Research in Surgical Oncology

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
January 01, 2002
End Date
August 31, 2021

Regional Oncolytic Poliovirus Immunotherapy for Breast Cancer

Administered By
Surgery, Surgical Sciences
AwardedBy
Department of Defense
Role
Co Investigator
Start Date
August 01, 2016
End Date
July 31, 2021

Genomic Diversity and the Microenvironment as Drivers of Progression in DCIS

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
Department of Defense
Role
Principal Investigator
Start Date
September 30, 2014
End Date
September 29, 2020

Characterization of Tumor Immunobiological Factors that Promote Lymphovascular Invasion and Dissemination in Locally Advanced Breast Cancer

Administered By
Surgery, Surgical Sciences
AwardedBy
Department of Defense
Role
Co Investigator
Start Date
August 15, 2017
End Date
August 14, 2020

Targeting DAMP-induced inflammation to prevent metastasis

Administered By
Surgery, Surgical Sciences
AwardedBy
Department of Defense
Role
Co Investigator
Start Date
September 30, 2016
End Date
September 29, 2019

NCI National Clinical Trials Network U10 (Year 4)

Administered By
Duke Cancer Institute
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
April 14, 2014
End Date
February 28, 2019

Comparing the Effectiveness of Guideline-concordant Care to Active Surveillance for DCIS: an Observational Study

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
Patient-Centered Outcomes Research Institute
Role
Principal Investigator
Start Date
November 01, 2015
End Date
January 31, 2019

Genetic testing for women with high-risk breast lesions

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
The Color Foundation
Role
Collaborating Investigator
Start Date
November 01, 2017
End Date
October 31, 2018

Molecular and Radiologic Predictors of Invasion in a DCIS Active Surveillance Cohort

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
Breast Cancer Research Foundation
Role
Principal Investigator
Start Date
October 01, 2016
End Date
September 30, 2018

Cancer Prevention Agent Development Program: Early Phase Clinical Research - CR

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
Northwestern University
Role
Principal Investigator
Start Date
September 15, 2016
End Date
September 14, 2018

Cancer Prevention Agent Development Program: Early Phase Clinical Research - FP

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
Northwestern University
Role
Principal Investigator
Start Date
September 15, 2016
End Date
September 14, 2018

The Mathematics of Breast Cancer Overtreatment: Improving Treatment Choice through Effective Communication of Personalized Cancer Risk

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 2016
End Date
August 31, 2018

(PQC3) Genomic Diversity and Microenvironment as Drivers of Metastasis in DCIS

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 2014
End Date
July 31, 2018

Genomic Health Oncotype DX DCIS Score

Administered By
Duke Cancer Institute
AwardedBy
Genomic Health
Role
Principal Investigator
Start Date
November 01, 2013
End Date
October 31, 2017

Optimizing Parameters and Techniques in Circulation Tumor Cell Collection (OPTICOLL)

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
University of Southern California
Role
Principal Investigator
Start Date
April 01, 2015
End Date
March 31, 2017

Preoperative Breast Radiotherapy: A Tool to Provide Individualized and Biologically-Based Radiation Therapy

Administered By
Radiation Oncology
AwardedBy
Gateway for Cancer Research
Role
Collaborator
Start Date
July 01, 2015
End Date
June 30, 2016

Optimizing Parameters and Techniques in Circulation Tumor Cell Collection (OPTICOLL)

Administered By
Surgery, Advanced Oncologic and Gastrointestinal Surgery
AwardedBy
Scripps Research Institute
Role
Principal Investigator
Start Date
February 05, 2013
End Date
November 30, 2014
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Publications:

Can algorithmically assessed MRI features predict which patients with a preoperative diagnosis of ductal carcinoma in situ are upstaged to invasive breast cancer?

To assess the ability of algorithmically assessed magnetic resonance imaging (MRI) features to predict the likelihood of upstaging to invasive cancer in newly diagnosed ductal carcinoma in situ (DCIS).We identified 131 patients at our institution from 2000-2014 with a core needle biopsy-confirmed diagnosis of pure DCIS, a 1.5 or 3T preoperative bilateral breast MRI with nonfat-saturated T1 -weighted MRI sequences, no preoperative therapy before breast MRI, and no prior history of breast cancer. A fellowship-trained radiologist identified the lesion on each breast MRI using a bounding box. Twenty-nine imaging features were then computed automatically using computer algorithms based on the radiologist's annotation.The rate of upstaging of DCIS to invasive cancer in our study was 26.7% (35/131). Out of all imaging variables tested, the information measure of correlation 1, which quantifies spatial dependency in neighboring voxels of the tumor, showed the highest predictive value of upstaging with an area under the curve (AUC) = 0.719 (95% confidence interval [CI]: 0.609-0.829). This feature was statistically significant after adjusting for tumor size (P < 0.001).Automatically assessed MRI features may have a role in triaging which patients with a preoperative diagnosis of DCIS are at highest risk for occult invasive disease.4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1332-1340.

Authors
Harowicz, MR; Saha, A; Grimm, LJ; Marcom, PK; Marks, JR; Hwang, ES; Mazurowski, MA
MLA Citation
Harowicz, MR, Saha, A, Grimm, LJ, Marcom, PK, Marks, JR, Hwang, ES, and Mazurowski, MA. "Can algorithmically assessed MRI features predict which patients with a preoperative diagnosis of ductal carcinoma in situ are upstaged to invasive breast cancer?." Journal of magnetic resonance imaging : JMRI 46.5 (November 2017): 1332-1340.
PMID
28181348
Source
epmc
Published In
Journal of Magnetic Resonance Imaging
Volume
46
Issue
5
Publish Date
2017
Start Page
1332
End Page
1340
DOI
10.1002/jmri.25655

Imaging Features of Patients Undergoing Active Surveillance for Ductal Carcinoma in Situ.

The aim of this study was to describe the imaging appearance of patients undergoing active surveillance for ductal carcinoma in situ (DCIS).We retrospectively identified 29 patients undergoing active surveillance for DCIS from 2009 to 2014. Twenty-two patients (group 1) refused surgery or were not surgical candidates. Seven patients (group 2) enrolled in a trial of letrozole and deferred surgical excision for 6-12 months. Pathology and imaging results at the initial biopsy and follow-up were recorded.In group 1, the median follow-up was 2.7 years (range: 0.6-13.9 years). Fifteen patients (68%) remained stable. Seven patients (32%) underwent additional biopsies with invasive ductal carcinoma diagnosed in two patients after 3.9 and 3.6 years who developed increasing calcifications and new masses. In group 2, one patient (14%) was upstaged to microinvasive ductal carcinoma at surgery. Among the patients in both groups with calcifications (n = 26), there was no progression to invasive disease among those with stable (50%, 13/26) or decreased (19%, 5/26) calcifications.Among a DCIS active surveillance cohort, invasive disease progression presented as increasing calcifications and a new mass following more than 3.5 years of stable imaging. In contrast, there was no progression to invasive disease among cases of DCIS with stable or decreasing calcifications. Close imaging is a key follow-up component in active surveillance.

Authors
Grimm, LJ; Ghate, SV; Hwang, ES; Soo, MS
MLA Citation
Grimm, LJ, Ghate, SV, Hwang, ES, and Soo, MS. "Imaging Features of Patients Undergoing Active Surveillance for Ductal Carcinoma in Situ." Academic radiology 24.11 (November 2017): 1364-1371.
PMID
28705686
Source
epmc
Published In
Academic Radiology
Volume
24
Issue
11
Publish Date
2017
Start Page
1364
End Page
1371
DOI
10.1016/j.acra.2017.05.017

Surgical Upstaging Rates for Vacuum Assisted Biopsy Proven DCIS: Implications for Active Surveillance Trials.

This study was designed to determine invasive cancer upstaging rates at surgical excision following vacuum-assisted biopsy of ductal carcinoma in situ (DCIS) among women meeting eligibility for active surveillance trials.Patients with vacuum-assisted, biopsy-proven DCIS at a single center from 2008 to 2015 were retrospectively reviewed. Imaging and pathology reports were interrogated for the imaging appearance, tumor grade, hormone receptor status, and presence of comedonecrosis. Subsequent surgical reports were reviewed for upstaging to invasive disease. Cases were classified by eligibility criteria for the COMET, LORIS, and LORD DCIS active surveillance trials.Of 307 DCIS diagnoses, 15 (5%) were low, 95 (31%) intermediate, and 197 (64%) high nuclear grade. The overall upstage rate to invasive disease was 17% (53/307). Eighty-one patients were eligible for the COMET Trial, 74 for the LORIS trial, and 10 for the LORD Trial, although LORIS trial eligibility also included real-time, multiple central pathology review, including elements not routinely reported. The upstaging rates to invasive disease were 6% (5/81), 7% (5/74), and 10% (1/10) for the COMET, LORIS, and LORD trials, respectively. Among upstaged cancers (n = 5), four tumors were Stage IA invasive ductal carcinoma and one was Stage IIA invasive lobular carcinoma; all were node-negative.DCIS upstaging rates in women eligible for active surveillance trials are low (6-10%), and in this series, all those with invasive disease were early-stage, node-negative. The careful patient selection for DCIS active surveillance trials has a low risk of missing occult invasive cancer and additional studies will determine clinical outcomes.

Authors
Grimm, LJ; Ryser, MD; Partridge, AH; Thompson, AM; Thomas, JS; Wesseling, J; Hwang, ES
MLA Citation
Grimm, LJ, Ryser, MD, Partridge, AH, Thompson, AM, Thomas, JS, Wesseling, J, and Hwang, ES. "Surgical Upstaging Rates for Vacuum Assisted Biopsy Proven DCIS: Implications for Active Surveillance Trials." Annals of surgical oncology 24.12 (November 2017): 3534-3540.
PMID
28795370
Source
epmc
Published In
Annals of Surgical Oncology
Volume
24
Issue
12
Publish Date
2017
Start Page
3534
End Page
3540
DOI
10.1245/s10434-017-6018-9

Patient Age and Tumor Subtype Predict the Extent of Axillary Surgery Among Breast Cancer Patients Eligible for the American College of Surgeons Oncology Group Trial Z0011.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial established the safety of omitting axillary lymph node dissection (ALND) for early-stage breast cancer patients with limited nodal disease undergoing lumpectomy. We examined the extent of axillary surgery among women eligible for Z0011 based on patient age and tumor subtype.Patients with cT1-2, cN0 breast cancers and one or two positive nodes diagnosed from 2009 to 2014 and treated with lumpectomy were identified in the National Cancer Data Base. Sentinel lymph node biopsy (SLNB) was defined as the removal of 1-5 nodes and ALND as the removal of 10 nodes or more. Tumor subtype was categorized as luminal, human epidermal growth factor 2-positive (HER2+), or triple-negative. Logistic regression was used to estimate the odds of receiving SLNB alone versus ALND.The inclusion criteria were met by 28,631 patients (21,029 SLNB-alone and 7602 ALND patients). Patients 70 years of age or older were more likely to undergo SLNB alone than ALND (27.0% vs 20.1%; p < 0.001). The radiation therapy use rate was 89.4% after SLNB alone and 89.7% after ALND. In the multivariate analysis, the uptake of Z0011 recommendations increased over time (2014 vs 2009: odds ratio [OR] 13.02; p < 0.001). Younger patients were less likely to undergo SLNB alone than older patients (age <40 vs ≥70: OR 0.59; p < 0.001). Patients with HER2+ (OR 0.89) or triple-negative disease (OR 0.79) (p < 0.001) were less likely to undergo SLNB alone than those with luminal subtypes.Among women potentially eligible for ACOSOG Z0011, the use of SLNB alone increased over time in all groups, but the extent of axillary surgery differed by patient age and tumor subtype.

Authors
Ong, CT; Thomas, SM; Blitzblau, RC; Fayanju, OM; Park, TS; Plichta, JK; Rosenberger, LH; Hyslop, T; Shelley Hwang, E; Greenup, RA
MLA Citation
Ong, CT, Thomas, SM, Blitzblau, RC, Fayanju, OM, Park, TS, Plichta, JK, Rosenberger, LH, Hyslop, T, Shelley Hwang, E, and Greenup, RA. "Patient Age and Tumor Subtype Predict the Extent of Axillary Surgery Among Breast Cancer Patients Eligible for the American College of Surgeons Oncology Group Trial Z0011." Annals of surgical oncology 24.12 (November 2017): 3559-3566.
PMID
28879416
Source
epmc
Published In
Annals of Surgical Oncology
Volume
24
Issue
12
Publish Date
2017
Start Page
3559
End Page
3566
DOI
10.1245/s10434-017-6075-0

Classifying the evolutionary and ecological features of neoplasms.

Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been proposed for drawing clinically relevant distinctions between how different tumours are evolving. On the basis of a consensus conference of experts in the fields of cancer evolution and cancer ecology, we propose a framework for classifying tumours that is based on four relevant components. These are the diversity of neoplastic cells (intratumoural heterogeneity) and changes over time in that diversity, which make up an evolutionary index (Evo-index), as well as the hazards to neoplastic cell survival and the resources available to neoplastic cells, which make up an ecological index (Eco-index). We review evidence demonstrating the importance of each of these factors and describe multiple methods that can be used to measure them. Development of this classification system holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient's tumour. The Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions, with potential implications for clinical trials, personalized medicine and basic cancer research.

Authors
Maley, CC; Aktipis, A; Graham, TA; Sottoriva, A; Boddy, AM; Janiszewska, M; Silva, AS; Gerlinger, M; Yuan, Y; Pienta, KJ; Anderson, KS; Gatenby, R; Swanton, C; Posada, D; Wu, C-I; Schiffman, JD; Hwang, ES; Polyak, K; Anderson, ARA; Brown, JS; Greaves, M; Shibata, D
MLA Citation
Maley, CC, Aktipis, A, Graham, TA, Sottoriva, A, Boddy, AM, Janiszewska, M, Silva, AS, Gerlinger, M, Yuan, Y, Pienta, KJ, Anderson, KS, Gatenby, R, Swanton, C, Posada, D, Wu, C-I, Schiffman, JD, Hwang, ES, Polyak, K, Anderson, ARA, Brown, JS, Greaves, M, and Shibata, D. "Classifying the evolutionary and ecological features of neoplasms." Nature reviews. Cancer 17.10 (October 2017): 605-619. (Review)
PMID
28912577
Source
epmc
Published In
Nature Reviews Cancer
Volume
17
Issue
10
Publish Date
2017
Start Page
605
End Page
619
DOI
10.1038/nrc.2017.69

Can Occult Invasive Disease in Ductal Carcinoma In Situ Be Predicted Using Computer-extracted Mammographic Features?

This study aimed to determine whether mammographic features assessed by radiologists and using computer algorithms are prognostic of occult invasive disease for patients showing ductal carcinoma in situ (DCIS) only in core biopsy.In this retrospective study, we analyzed data from 99 subjects with DCIS (74 pure DCIS, 25 DCIS with occult invasion). We developed a computer-vision algorithm capable of extracting 113 features from magnification views in mammograms and combining these features to predict whether a DCIS case will be upstaged to invasive cancer at the time of definitive surgery. In comparison, we also built predictive models based on physician-interpreted features, which included histologic features extracted from biopsy reports and Breast Imaging Reporting and Data System-related mammographic features assessed by two radiologists. The generalization performance was assessed using leave-one-out cross validation with the receiver operating characteristic curve analysis.Using the computer-extracted mammographic features, the multivariate classifier was able to distinguish DCIS with occult invasion from pure DCIS, with an area under the curve for receiver operating characteristic equal to 0.70 (95% confidence interval: 0.59-0.81). The physician-interpreted features including histologic features and Breast Imaging Reporting and Data System-related mammographic features assessed by two radiologists showed mixed results, and only one radiologist's subjective assessment was predictive, with an area under the curve for receiver operating characteristic equal to 0.68 (95% confidence interval: 0.57-0.81).Predicting upstaging for DCIS based upon mammograms is challenging, and there exists significant interobserver variability among radiologists. However, the proposed computer-extracted mammographic features are promising for the prediction of occult invasion in DCIS.

Authors
Shi, B; Grimm, LJ; Mazurowski, MA; Baker, JA; Marks, JR; King, LM; Maley, CC; Hwang, ES; Lo, JY
MLA Citation
Shi, B, Grimm, LJ, Mazurowski, MA, Baker, JA, Marks, JR, King, LM, Maley, CC, Hwang, ES, and Lo, JY. "Can Occult Invasive Disease in Ductal Carcinoma In Situ Be Predicted Using Computer-extracted Mammographic Features?." Academic radiology 24.9 (September 2017): 1139-1147.
PMID
28506510
Source
epmc
Published In
Academic Radiology
Volume
24
Issue
9
Publish Date
2017
Start Page
1139
End Page
1147
DOI
10.1016/j.acra.2017.03.013

The Financial Burden of Breast Cancer Treatment

Authors
Greenup, RA; Fish, L; Rushing, C; Peppercorn, J; Hyslop, T; Zafar, Y; Hwang, ES
MLA Citation
Greenup, RA, Fish, L, Rushing, C, Peppercorn, J, Hyslop, T, Zafar, Y, and Hwang, ES. "The Financial Burden of Breast Cancer Treatment." September 2017.
Source
wos-lite
Published In
Journal of Women's Health
Volume
26
Issue
9
Publish Date
2017
Start Page
1022
End Page
1022

Reporting and Guidelines in Propensity Score Analysis: A Systematic Review of Cancer and Cancer Surgical Studies.

: Propensity score (PS) analysis is increasingly being used in observational studies, especially in some cancer studies where random assignment is not feasible. This systematic review evaluates the use and reporting quality of PS analysis in oncology studies.: We searched PubMed to identify the use of PS methods in cancer studies (CS) and cancer surgical studies (CSS) in major medical, cancer, and surgical journals over time and critically evaluated 33 CS published in top medical and cancer journals in 2014 and 2015 and 306 CSS published up to November 26, 2015, without earlier date limits. The quality of reporting in PS analysis was evaluated. It was also compared over time and among journals with differing impact factors. All statistical tests were two-sided.More than 50% of the publications with PS analysis from the past decade occurred within the past two years. Of the studies critically evaluated, a considerable proportion did not clearly provide the variables used to estimate PS (CS 12.1%, CSS 8.8%), incorrectly included non baseline variables (CS 3.4%, CSS 9.3%), neglected the comparison of baseline characteristics (CS 21.9%, CSS 15.6%), or did not report the matching algorithm utilized (CS 19.0%, CSS 36.1%). In CSS, the reporting of the matching algorithm improved in 2014 and 2015 ( P  = .04), and the reporting of variables used to estimate PS was better in top surgery journals ( P  = .008). However, there were no statistically significant differences for the inclusion of non baseline variables and reporting of comparability of baseline characteristics.The use of PS in cancer studies has dramatically increased recently, but there is substantial room for improvement in the quality of reporting even in top journals. Herein we have proposed reporting guidelines for PS analyses that are broadly applicable to different areas of medical research that will allow better evaluation and comparison across studies applying this approach.

Authors
Yao, XI; Wang, X; Speicher, PJ; Hwang, ES; Cheng, P; Harpole, DH; Berry, MF; Schrag, D; Pang, HH
MLA Citation
Yao, XI, Wang, X, Speicher, PJ, Hwang, ES, Cheng, P, Harpole, DH, Berry, MF, Schrag, D, and Pang, HH. "Reporting and Guidelines in Propensity Score Analysis: A Systematic Review of Cancer and Cancer Surgical Studies." Journal of the National Cancer Institute 109.8 (August 2017). (Review)
PMID
28376195
Source
epmc
Published In
Journal of the National Cancer Institute
Volume
109
Issue
8
Publish Date
2017
DOI
10.1093/jnci/djw323

Cost Effectiveness of Risk-Reducing Mastectomy versus Surveillance in BRCA Mutation Carriers with a History of Ovarian Cancer.

The appropriate management of breast cancer risk in BRCA mutation carriers following ovarian cancer diagnosis remains unclear. We sought to determine the survival benefit and cost effectiveness of risk-reducing mastectomy (RRM) among women with BRCA1/2 mutations following stage II-IV ovarian cancer.We constructed a decision model from a third-party payer perspective to compare annual screening with magnetic resonance imaging (MRI) and mammography to annual screening followed by RRM with reconstruction following ovarian cancer diagnosis. Survival, overall costs, and cost effectiveness were determined by decade at diagnosis using 2015 US dollars. All inputs were obtained from the literature and public databases. Monte Carlo probabilistic sensitivity analysis was performed with a $100,000 willingness-to-pay threshold.The incremental cost-effectiveness ratio (ICER) per year of life saved (YLS) for RRM increased with age and BRCA2 mutation status, with greater survival benefit demonstrated in younger patients with BRCA1 mutations. RRM delayed 5 years in 40-year-old BRCA1 mutation carriers was associated with 5 months of life gained (ICER $72,739/YLS), and in 60-year-old BRCA2 mutation carriers was associated with 0.8 months of life gained (ICER $334,906/YLS). In all scenarios, $/YLS and mastectomies per breast cancer prevented were lowest with RRM performed 5-10 years after ovarian cancer diagnosis.For most BRCA1/2 mutation carriers following ovarian cancer diagnosis, RRM performed within 5 years is not cost effective when compared with breast cancer screening. Imaging surveillance should be advocated during the first several years after ovarian cancer diagnosis, after which point the benefits of RRM can be considered based on patient age and BRCA mutation status.

Authors
Gamble, C; Havrilesky, LJ; Myers, ER; Chino, JP; Hollenbeck, S; Plichta, JK; Kelly Marcom, P; Shelley Hwang, E; Kauff, ND; Greenup, RA
MLA Citation
Gamble, C, Havrilesky, LJ, Myers, ER, Chino, JP, Hollenbeck, S, Plichta, JK, Kelly Marcom, P, Shelley Hwang, E, Kauff, ND, and Greenup, RA. "Cost Effectiveness of Risk-Reducing Mastectomy versus Surveillance in BRCA Mutation Carriers with a History of Ovarian Cancer." Annals of surgical oncology (July 11, 2017).
PMID
28699130
Source
epmc
Published In
Annals of Surgical Oncology
Publish Date
2017
DOI
10.1245/s10434-017-5995-z

Fat Grafting-More Than Just the Hype.

Authors
Hollenbeck, ST; Hwang, ES
MLA Citation
Hollenbeck, ST, and Hwang, ES. "Fat Grafting-More Than Just the Hype." JAMA surgery (June 28, 2017).
PMID
28658466
Source
epmc
Published In
JAMA Surgery
Publish Date
2017
DOI
10.1001/jamasurg.2017.1717

Suspicious breast calcifications undergoing stereotactic biopsy in women ages 70 and over: Breast cancer incidence by BI-RADS descriptors.

To determine the malignancy rate overall and for specific BI-RADS descriptors in women ≥70 years who undergo stereotactic biopsy for calcifications.We retrospectively reviewed 14,577 consecutive mammogram reports in 6839 women ≥70 years to collect 231 stereotactic biopsies of calcifications in 215 women. Cases with missing images or histopathology and calcifications associated with masses, distortion, or asymmetries were excluded. Three breast radiologists determined BI-RADS descriptors by majority. Histology, hormone receptor status, and lymph node status were correlated with BI-RADS descriptors.There were 131 (57 %) benign, 22 (10 %) atypia/lobular carcinomas in situ, 55 (24 %) ductal carcinomas in situ (DCIS), and 23 (10 %) invasive diagnoses. Twenty-seven (51 %) DCIS cases were high-grade. Five (22 %) invasive cases were high-grade, two (9 %) were triple-negative, and three (12 %) were node-positive. Malignancy was found in 49 % (50/103) of fine pleomorphic, 50 % (14/28) of fine linear, 25 % (10/40) of amorphous, 20 % (3/15) of round, 3 % (1/36) of coarse heterogeneous, and 0 % (0/9) of dystrophic calcifications.Among women ≥70 years that underwent stereotactic biopsy for calcifications only, we observed a high rate of malignancy. Additionally, coarse heterogeneous calcifications may warrant a probable benign designation.• Cancer rates of biopsied calcifications in women ≥70 years are high • Radiologists should not dismiss suspicious calcifications in older women • Coarse heterogeneous calcifications may warrant a probable benign designation.

Authors
Grimm, LJ; Johnson, DY; Johnson, KS; Baker, JA; Soo, MS; Hwang, ES; Ghate, SV
MLA Citation
Grimm, LJ, Johnson, DY, Johnson, KS, Baker, JA, Soo, MS, Hwang, ES, and Ghate, SV. "Suspicious breast calcifications undergoing stereotactic biopsy in women ages 70 and over: Breast cancer incidence by BI-RADS descriptors." European radiology 27.6 (June 2017): 2275-2281.
PMID
27752832
Source
epmc
Published In
European Radiology
Volume
27
Issue
6
Publish Date
2017
Start Page
2275
End Page
2281
DOI
10.1007/s00330-016-4617-7

Breast Cancer after Augmentation: Oncologic and Reconstructive Considerations among Women Undergoing Mastectomy.

Breast augmentation with subglandular versus subpectoral implants may differentially impact the early detection of breast cancer and treatment recommendations. The authors assessed the impact of prior augmentation on the diagnosis and management of breast cancer in women undergoing mastectomy.Breast cancer diagnosis and management were retrospectively analyzed in all women with prior augmentation undergoing therapeutic mastectomy at the authors' institution from 1993 to 2014. Comparison was made to all women with no prior augmentation undergoing mastectomy in 2010. Subanalyses were performed according to prior implant placement.A total of 260 women with (n = 89) and without (n = 171) prior augmentation underwent mastectomy for 95 and 179 breast cancers, respectively. Prior implant placement was subglandular (n = 27) or subpectoral (n = 63) (For five breasts, the placement was unknown). Breast cancer stage at diagnosis (p = 0.19) and detection method (p = 0.48) did not differ for women with and without prior augmentation. Compared to subpectoral augmentation, subglandular augmentation was associated with the diagnosis of invasive breast cancer rather than ductal carcinoma in situ (p = 0.01) and detection by self-palpation rather than screening mammography (p = 0.03). Immediate two-stage implant reconstruction was the preferred reconstructive method in women with augmentation (p < 0.01).Breast cancer stage at diagnosis was similar for women with and without prior augmentation. Among women with augmentation, however, subglandular implants were associated with more advanced breast tumors commonly detected on palpation rather than mammography. Increased vigilance in breast cancer screening is recommended among women with subglandular augmentation.Therapeutic, III.

Authors
Cho, EH; Shammas, RL; Phillips, BT; Greenup, RA; Hwang, ES; Hollenbeck, ST
MLA Citation
Cho, EH, Shammas, RL, Phillips, BT, Greenup, RA, Hwang, ES, and Hollenbeck, ST. "Breast Cancer after Augmentation: Oncologic and Reconstructive Considerations among Women Undergoing Mastectomy." Plastic and reconstructive surgery 139.6 (June 2017): 1240e-1249e.
PMID
28538550
Source
epmc
Published In
Plastic and Reconstructive Surgery
Volume
139
Issue
6
Publish Date
2017
Start Page
1240e
End Page
1249e
DOI
10.1097/prs.0000000000003342

Reply to L.B. Marks et al.

Authors
Recht, A; Comen, EA; Fine, RE; Fleming, GF; Hardenbergh, PH; Ho, AY; Hudis, CA; Hwang, ES; Kirshner, JJ; Morrow, M; Salerno, KE; Sledge, GW; Solin, LJ; Spears, PA; Whelan, TJ; Somerfield, MR; Edge, SB
MLA Citation
Recht, A, Comen, EA, Fine, RE, Fleming, GF, Hardenbergh, PH, Ho, AY, Hudis, CA, Hwang, ES, Kirshner, JJ, Morrow, M, Salerno, KE, Sledge, GW, Solin, LJ, Spears, PA, Whelan, TJ, Somerfield, MR, and Edge, SB. "Reply to L.B. Marks et al." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 35.11 (April 2017): 1258-1259.
PMID
28068171
Source
epmc
Published In
Journal of Clinical Oncology
Volume
35
Issue
11
Publish Date
2017
Start Page
1258
End Page
1259
DOI
10.1200/jco.2016.71.3966

Cost Implications of an Evidence-Based Approach to Radiation Treatment After Lumpectomy for Early-Stage Breast Cancer.

Breast cancer treatment costs are rising, and identification of high-value oncology treatment strategies is increasingly needed. We sought to determine the potential cost savings associated with an evidence-based radiation treatment (RT) approach among women with early-stage breast cancer treated in the United States.Using the National Cancer Database, we identified women with T1-T2 N0 invasive breast cancers treated with lumpectomy during 2011. Adjuvant RT regimens were categorized as conventionally fractionated whole-breast irradiation, hypofractionated whole-breast irradiation, and omission of RT. National RT patterns were determined, and RT costs were estimated using the Medicare Physician Fee Schedule.Within the 43,247 patient cohort, 64% (n = 27,697) received conventional RT, 13.3% (n = 5,724) received hypofractionated RT, 1.1% (n = 477) received accelerated partial-breast irradiation, and 21.6% (n = 9,349) received no RT. Among patients who were eligible for shorter RT or omission of RT, 57% underwent treatment with longer, more costly regimens. Estimated RT expenditures of the national cohort approximated $420.2 million during 2011, compared with $256.2 million had women been treated with the least expensive regimens for which they were safely eligible. This demonstrated a potential annual savings of $164.0 million, a 39% reduction in associated treatment costs.Among women with early-stage breast cancer after lumpectomy, use of an evidence-based approach illustrates an example of high-value care within oncology. Identification of high-value cancer treatment strategies is critically important to maintaining excellence in cancer care while reducing health care expenditures.

Authors
Greenup, RA; Blitzblau, RC; Houck, KL; Sosa, JA; Horton, J; Peppercorn, JM; Taghian, AG; Smith, BL; Hwang, ES
MLA Citation
Greenup, RA, Blitzblau, RC, Houck, KL, Sosa, JA, Horton, J, Peppercorn, JM, Taghian, AG, Smith, BL, and Hwang, ES. "Cost Implications of an Evidence-Based Approach to Radiation Treatment After Lumpectomy for Early-Stage Breast Cancer." Journal of oncology practice 13.4 (April 2017): e283-e290.
PMID
28291382
Source
epmc
Published In
Journal of Oncology Practice
Volume
13
Issue
4
Publish Date
2017
Start Page
e283
End Page
e290
DOI
10.1200/jop.2016.016683

What Can Molecular Diagnostics Add to Locoregional Treatment Recommendations for DCIS?

Authors
Shelley Hwang, E; Thompson, A
MLA Citation
Shelley Hwang, E, and Thompson, A. "What Can Molecular Diagnostics Add to Locoregional Treatment Recommendations for DCIS?." Journal of the National Cancer Institute 109.4 (April 2017).
PMID
28376162
Source
epmc
Published In
Journal of the National Cancer Institute
Volume
109
Issue
4
Publish Date
2017
DOI
10.1093/jnci/djw270

Clinical Utility of the 12-Gene DCIS Score Assay: Impact on Radiotherapy Recommendations for Patients with Ductal Carcinoma In Situ.

The aim of this study was to determine the impact of the results of the 12-gene DCIS Score assay on (i) radiotherapy recommendations for patients with pure ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), and (ii) patient decisional conflict and state anxiety.Thirteen sites across the US enrolled patients (March 2014-August 2015) with pure DCIS undergoing BCS. Prospectively collected data included clinicopathologic factors, physician estimates of local recurrence risk, DCIS Score results, and pre-/post-assay radiotherapy recommendations for each patient made by a surgeon and a radiation oncologist. Patients completed pre-/post-assay decisional conflict scale and state-trait anxiety inventory instruments.The analysis cohort included 127 patients: median age 60 years, 80 % postmenopausal, median size 8 mm (39 % ≤5 mm), 70 % grade 1/2, 88 % estrogen receptor-positive, 75 % progesterone receptor-positive, 54 % with comedo necrosis, and 18 % multifocal. Sixty-six percent of patients had low DCIS Score results, 20 % had intermediate DCIS Score results, and 14 % had high DCIS Score results; the median result was 21 (range 0-84). Pre-assay, surgeons and radiation oncologists recommended radiotherapy for 70.9 and 72.4 % of patients, respectively. Post-assay, 26.4 % of overall recommendations changed, including 30.7 and 22.0 % of recommendations by surgeons and radiation oncologists, respectively. Among patients with confirmed completed questionnaires (n = 32), decision conflict (p = 0.004) and state anxiety (p = 0.042) decreased significantly from pre- to post-assay.Individualized risk estimates from the DCIS Score assay provide valuable information to physicians and patients. Post-assay, in response to DCIS Score results, surgeons changed treatment recommendations more often than radiation oncologists. Further investigation is needed to better understand how such treatment changes may affect clinical outcomes.

Authors
Manders, JB; Kuerer, HM; Smith, BD; McCluskey, C; Farrar, WB; Frazier, TG; Li, L; Leonard, CE; Carter, DL; Chawla, S; Medeiros, LE; Guenther, JM; Castellini, LE; Buchholz, DJ; Mamounas, EP; Wapnir, IL; Horst, KC; Chagpar, A; Evans, SB; Riker, AI; Vali, FS; Solin, LJ; Jablon, L; Recht, A; Sharma, R; Lu, R; Sing, AP; Hwang, ES; White, J; Study investigators and study participants,
MLA Citation
Manders, JB, Kuerer, HM, Smith, BD, McCluskey, C, Farrar, WB, Frazier, TG, Li, L, Leonard, CE, Carter, DL, Chawla, S, Medeiros, LE, Guenther, JM, Castellini, LE, Buchholz, DJ, Mamounas, EP, Wapnir, IL, Horst, KC, Chagpar, A, Evans, SB, Riker, AI, Vali, FS, Solin, LJ, Jablon, L, Recht, A, Sharma, R, Lu, R, Sing, AP, Hwang, ES, White, J, and Study investigators and study participants, . "Clinical Utility of the 12-Gene DCIS Score Assay: Impact on Radiotherapy Recommendations for Patients with Ductal Carcinoma In Situ." Annals of surgical oncology 24.3 (March 2017): 660-668.
PMID
27704370
Source
epmc
Published In
Annals of Surgical Oncology
Volume
24
Issue
3
Publish Date
2017
Start Page
660
End Page
668
DOI
10.1245/s10434-016-5583-7

Contralateral Prophylactic Mastectomy: Aligning Patient Preferences and Provider Recommendations.

Authors
Fayanju, OM; Hwang, ES
MLA Citation
Fayanju, OM, and Hwang, ES. "Contralateral Prophylactic Mastectomy: Aligning Patient Preferences and Provider Recommendations." JAMA surgery 152.3 (March 2017): 282-283.
PMID
28002558
Source
epmc
Published In
JAMA Surgery
Volume
152
Issue
3
Publish Date
2017
Start Page
282
End Page
283
DOI
10.1001/jamasurg.2016.4750

Value of Propensity Score Matching to Study Surgical Outcomes.

Authors
Hwang, ES; Wang, X
MLA Citation
Hwang, ES, and Wang, X. "Value of Propensity Score Matching to Study Surgical Outcomes." Annals of surgery 265.3 (March 2017): 457-458.
PMID
28045717
Source
epmc
Published In
Annals of Surgery
Volume
265
Issue
3
Publish Date
2017
Start Page
457
End Page
458
DOI
10.1097/sla.0000000000002125

Abstract P1-06-06: Evidence for tumor heterogeneity and clonal evolution during invasive progression of breast cancer

Authors
Ding, Y; Marks, JR; King, LM; Hall, AH; Mardis, ER; Rodrigo, AG; Maley, CC; Hwang, E-S
MLA Citation
Ding, Y, Marks, JR, King, LM, Hall, AH, Mardis, ER, Rodrigo, AG, Maley, CC, and Hwang, E-S. "Abstract P1-06-06: Evidence for tumor heterogeneity and clonal evolution during invasive progression of breast cancer." February 15, 2017.
Source
crossref
Published In
Cancer Research
Volume
77
Issue
4 Supplement
Publish Date
2017
Start Page
P1-06-06
End Page
P1-06-06
DOI
10.1158/1538-7445.SABCS16-P1-06-06

H3K27me3 Expression and X Chromosome Inactivation in Breast Carcinoma

Authors
Bean, G; Pekmezci, M; Chen, Y-Y; Hwang, ES; Krings, G
MLA Citation
Bean, G, Pekmezci, M, Chen, Y-Y, Hwang, ES, and Krings, G. "H3K27me3 Expression and X Chromosome Inactivation in Breast Carcinoma." February 2017.
Source
wos-lite
Published In
Laboratory Investigation
Volume
97
Publish Date
2017
Start Page
32A
End Page
32A

H3K27me3 Expression and X Chromosome Inactivation in Breast Carcinoma

Authors
Bean, G; Pekmezci, M; Chen, Y-Y; Hwang, ES; Krings, G
MLA Citation
Bean, G, Pekmezci, M, Chen, Y-Y, Hwang, ES, and Krings, G. "H3K27me3 Expression and X Chromosome Inactivation in Breast Carcinoma." February 2017.
Source
wos-lite
Published In
Modern Pathology
Volume
30
Publish Date
2017
Start Page
32A
End Page
32A

Prediction of occult invasive disease in ductal carcinoma in situ using computer-extracted mammographic features

© 2017 SPIE. Predicting the risk of occult invasive disease in ductal carcinoma in situ (DCIS) is an important task to help address the overdiagnosis and overtreatment problems associated with breast cancer. In this work, we investigated the feasibility of using computer-extracted mammographic features to predict occult invasive disease in patients with biopsy proven DCIS. We proposed a computer-vision algorithm based approach to extract mammographic features from magnification views of full field digital mammography (FFDM) for patients with DCIS. After an expert breast radiologist provided a region of interest (ROI) mask for the DCIS lesion, the proposed approach is able to segment individual microcalcifications (MCs), detect the boundary of the MC cluster (MCC), and extract 113 mammographic features from MCs and MCC within the ROI. In this study, we extracted mammographic features from 99 patients with DCIS (74 pure DCIS; 25 DCIS plus invasive disease). The predictive power of the mammographic features was demonstrated through binary classifications between pure DCIS and DCIS with invasive disease using linear discriminant analysis (LDA). Before classification, the minimum redundancy Maximum Relevance (mRMR) feature selection method was first applied to choose subsets of useful features. The generalization performance was assessed using Leave-One-Out Cross-Validation and Receiver Operating Characteristic (ROC) curve analysis. Using the computer-extracted mammographic features, the proposed model was able to distinguish DCIS with invasive disease from pure DCIS, with an average classification performance of AUC = 0.61 ± 0.05. Overall, the proposed computer-extracted mammographic features are promising for predicting occult invasive disease in DCIS.

Authors
Shi, B; Grimm, LJ; Mazurowski, MA; Marks, JR; King, LM; Maley, CC; Hwang, ES; Lo, JY
MLA Citation
Shi, B, Grimm, LJ, Mazurowski, MA, Marks, JR, King, LM, Maley, CC, Hwang, ES, and Lo, JY. "Prediction of occult invasive disease in ductal carcinoma in situ using computer-extracted mammographic features." January 1, 2017.
Source
scopus
Published In
Proceedings of SPIE
Volume
10134
Publish Date
2017
DOI
10.1117/12.2255731

Can upstaging of ductal carcinoma in situ be predicted at biopsy by histologic and mammographic features?

© 2017 SPIE. Reducing the overdiagnosis and overtreatment associated with ductal carcinoma in situ (DCIS) requires accurate prediction of the invasive potential at cancer screening. In this work, we investigated the utility of pre-operative histologic and mammographic features to predict upstaging of DCIS. The goal was to provide intentionally conservative baseline performance using readily available data from radiologists and pathologists and only linear models. We conducted a retrospective analysis on 99 patients with DCIS. Of those 25 were upstaged to invasive cancer at the time of definitive surgery. Pre-operative factors including both the histologic features extracted from stereotactic core needle biopsy (SCNB) reports and the mammographic features annotated by an expert breast radiologist were investigated with statistical analysis. Furthermore, we built classification models based on those features in an attempt to predict the presence of an occult invasive component in DCIS, with generalization performance assessed by receiver operating characteristic (ROC) curve analysis. Histologic features including nuclear grade and DCIS subtype did not show statistically significant differences between cases with pure DCIS and with DCIS plus invasive disease. However, three mammographic features, i.e., the major axis length of DCIS lesion, the BI-RADS level of suspicion, and radiologist's assessment did achieve the statistical significance. Using those three statistically significant features as input, a linear discriminant model was able to distinguish patients with DCIS plus invasive disease from those with pure DCIS, with AUC-ROC equal to 0.62. Overall, mammograms used for breast screening contain useful information that can be perceived by radiologists and help predict occult invasive components in DCIS.

Authors
Shi, B; Grimm, LJ; Mazurowski, MA; Marks, JR; King, LM; Maley, CC; Hwang, ES; Lo, JY
MLA Citation
Shi, B, Grimm, LJ, Mazurowski, MA, Marks, JR, King, LM, Maley, CC, Hwang, ES, and Lo, JY. "Can upstaging of ductal carcinoma in situ be predicted at biopsy by histologic and mammographic features?." January 1, 2017.
Source
scopus
Published In
Proceedings of SPIE
Volume
10134
Publish Date
2017
DOI
10.1117/12.2255847

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update.

A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT).A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data.The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Authors
Recht, A; Comen, EA; Fine, RE; Fleming, GF; Hardenbergh, PH; Ho, AY; Hudis, CA; Hwang, ES; Kirshner, JJ; Morrow, M; Salerno, KE; Sledge, GW; Solin, LJ; Spears, PA; Whelan, TJ; Somerfield, MR; Edge, SB
MLA Citation
Recht, A, Comen, EA, Fine, RE, Fleming, GF, Hardenbergh, PH, Ho, AY, Hudis, CA, Hwang, ES, Kirshner, JJ, Morrow, M, Salerno, KE, Sledge, GW, Solin, LJ, Spears, PA, Whelan, TJ, Somerfield, MR, and Edge, SB. "Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update." Annals of surgical oncology 24.1 (January 2017): 38-51.
PMID
27646018
Source
epmc
Published In
Annals of Surgical Oncology
Volume
24
Issue
1
Publish Date
2017
Start Page
38
End Page
51
DOI
10.1245/s10434-016-5558-8

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update.

Purpose A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). Methods A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. Recommendations The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Authors
Recht, A; Comen, EA; Fine, RE; Fleming, GF; Hardenbergh, PH; Ho, AY; Hudis, CA; Hwang, ES; Kirshner, JJ; Morrow, M; Salerno, KE; Sledge, GW; Solin, LJ; Spears, PA; Whelan, TJ; Somerfield, MR; Edge, SB
MLA Citation
Recht, A, Comen, EA, Fine, RE, Fleming, GF, Hardenbergh, PH, Ho, AY, Hudis, CA, Hwang, ES, Kirshner, JJ, Morrow, M, Salerno, KE, Sledge, GW, Solin, LJ, Spears, PA, Whelan, TJ, Somerfield, MR, and Edge, SB. "Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.36 (December 2016): 4431-4442. (Review)
PMID
27646947
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
36
Publish Date
2016
Start Page
4431
End Page
4442
DOI
10.1200/jco.2016.69.1188

Reply to J. Heil et al.

Authors
Hwang, ES; Hyslop, T
MLA Citation
Hwang, ES, and Hyslop, T. "Reply to J. Heil et al." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.34 (December 2016): 4192-.
PMID
27621401
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
34
Publish Date
2016
Start Page
4192
DOI
10.1200/jco.2016.69.1121

Active Surveillance for DCIS: The Importance of Selection Criteria and Monitoring.

Authors
Grimm, LJ; Shelley Hwang, E
MLA Citation
Grimm, LJ, and Shelley Hwang, E. "Active Surveillance for DCIS: The Importance of Selection Criteria and Monitoring." Annals of surgical oncology 23.13 (December 2016): 4134-4136.
PMID
27704372
Source
epmc
Published In
Annals of Surgical Oncology
Volume
23
Issue
13
Publish Date
2016
Start Page
4134
End Page
4136
DOI
10.1245/s10434-016-5596-2

Comparing Coordinated Versus Sequential Salpingo-Oophorectomy for BRCA1 and BRCA2 Mutation Carriers With Breast Cancer.

Women with breast cancer who carry BRCA1 or BRCA2 mutations must also consider risk-reducing salpingo-oophorectomy (RRSO) and how to coordinate this procedure with their breast surgery. We report the factors associated with coordinated versus sequential surgery and compare the outcomes of each.Patients in our cancer risk database who had breast cancer and a known deleterious BRCA1/2 mutation before undergoing breast surgery were included. Women who chose concurrent RRSO at the time of breast surgery were compared to those who did not.Sixty-two patients knew their mutation carrier status before undergoing breast cancer surgery. Forty-three patients (69%) opted for coordinated surgeries, and 19 (31%) underwent sequential surgeries at a median follow-up of 4.4 years. Women who underwent coordinated surgery were significantly older than those who chose sequential surgery (median age of 45 vs. 39 years; P = .025). There were no differences in comorbidities between groups. Patients who received neoadjuvant chemotherapy were more likely to undergo coordinated surgery (65% vs. 37%; P = .038). Sequential surgery patients had longer hospital stays (4.79 vs. 3.44 days, P = .01) and longer operating times (8.25 vs. 6.38 hours, P = .006) than patients who elected combined surgery. Postoperative complications were minor and were no more likely in either group (odds ratio, 4.76; 95% confidence interval, 0.56-40.6).Coordinating RRSO with breast surgery is associated with receipt of neoadjuvant chemotherapy, longer operating times, and hospital stays without an observed increase in complications. In the absence of risk, surgical options can be personalized.

Authors
S Chapman, J; Roddy, E; Panighetti, A; Hwang, S; Crawford, B; Powell, B; Chen, L-M
MLA Citation
S Chapman, J, Roddy, E, Panighetti, A, Hwang, S, Crawford, B, Powell, B, and Chen, L-M. "Comparing Coordinated Versus Sequential Salpingo-Oophorectomy for BRCA1 and BRCA2 Mutation Carriers With Breast Cancer." Clinical breast cancer 16.6 (December 2016): 494-499.
PMID
27495996
Source
epmc
Published In
Clinical Breast Cancer
Volume
16
Issue
6
Publish Date
2016
Start Page
494
End Page
499
DOI
10.1016/j.clbc.2016.06.016

DCIS-Conservative Nonsurgical Management- The Problem of Over-diagnosis: What is the Path Forward?

Authors
Hwang, ES
MLA Citation
Hwang, ES. "DCIS-Conservative Nonsurgical Management- The Problem of Over-diagnosis: What is the Path Forward?." December 2016.
Source
wos-lite
Published In
Menopause
Volume
23
Issue
12
Publish Date
2016
Start Page
1365
End Page
1365

The Effect of Hospital Volume on Breast Cancer Mortality.

The aim of this study was to determine whether hospital volume was associated with mortality in breast cancer, and what thresholds of case volume impacted survival.Prior literature has demonstrated improved survival with treatment at high volume centers among less common cancers requiring technically complex surgery.All adults (18 to 90 years) with stages 0-III unilateral breast cancer diagnosed from 2004 to 2012 were identified from the American College of Surgeons National Cancer Data Base (NCDB). A multivariable Cox proportional hazards model with restricted cubic splines was used to examine the association of annual hospital volume and overall survival, after adjusting for measured covariates. Intergroup comparisons of patient and treatment characteristics were conducted with X and analysis of variance (ANOVA). The log-rank test was used to test survival differences between groups. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HRs) associated with each volume group.One million sixty-four thousand two hundred and fifty-one patients met inclusion criteria. The median age of the sample was 60 (interquartile range 50 to 70). Hospitals were categorized into 3 groups using restricted cubic spline analysis: low-volume (<148 cases/year), moderate-volume (148 to 298 cases/year), and high-volume (>298 cases/year). Treatment at high volume centers was associated with an 11% reduction in overall mortality for all patients (HR 0.89); those with stage 0-I, ER+/PR+ or ER+/PR- breast cancers derived the greatest benefit.Treatment at high volume centers is associated with improved survival for breast cancer patients regardless of stage. High case volume could serve as a proxy for the institutional infrastructure required to deliver complex multidisciplinary breast cancer treatment.

Authors
Greenup, RA; Obeng-Gyasi, S; Thomas, S; Houck, K; Lane, WO; Blitzblau, RC; Hyslop, T; Hwang, ES
MLA Citation
Greenup, RA, Obeng-Gyasi, S, Thomas, S, Houck, K, Lane, WO, Blitzblau, RC, Hyslop, T, and Hwang, ES. "The Effect of Hospital Volume on Breast Cancer Mortality." Annals of surgery (November 23, 2016).
PMID
27893532
Source
epmc
Published In
Annals of Surgery
Publish Date
2016

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update.

A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT).A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data.The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Authors
Recht, A; Comen, EA; Fine, RE; Fleming, GF; Hardenbergh, PH; Ho, AY; Hudis, CA; Hwang, ES; Kirshner, JJ; Morrow, M; Salerno, KE; Sledge, GW; Solin, LJ; Spears, PA; Whelan, TJ; Somerfield, MR; Edge, SB
MLA Citation
Recht, A, Comen, EA, Fine, RE, Fleming, GF, Hardenbergh, PH, Ho, AY, Hudis, CA, Hwang, ES, Kirshner, JJ, Morrow, M, Salerno, KE, Sledge, GW, Solin, LJ, Spears, PA, Whelan, TJ, Somerfield, MR, and Edge, SB. "Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update." Practical radiation oncology 6.6 (November 2016): e219-e234. (Review)
PMID
27659727
Source
epmc
Published In
Practical Radiation Oncology
Volume
6
Issue
6
Publish Date
2016
Start Page
e219
End Page
e234
DOI
10.1016/j.prro.2016.08.009

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ.

Background Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation (WBRT). Methods A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus. Results Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2 mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2 mm margins. Negative margins less than 2 mm alone are not an indication for mastectomy, and factors known to impact rates of IBTR should be considered in determining the need for re-excision. Conclusion The use of a 2 mm margin as the standard for an adequate margin in DCIS treated with WBRT is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcome, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins < 2 mm.

Authors
Morrow, M; Van Zee, KJ; Solin, LJ; Houssami, N; Chavez-MacGregor, M; Harris, JR; Horton, J; Hwang, S; Johnson, PL; Marinovich, ML; Schnitt, SJ; Wapnir, I; Moran, MS
MLA Citation
Morrow, M, Van Zee, KJ, Solin, LJ, Houssami, N, Chavez-MacGregor, M, Harris, JR, Horton, J, Hwang, S, Johnson, PL, Marinovich, ML, Schnitt, SJ, Wapnir, I, and Moran, MS. "Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.33 (November 2016): 4040-4046.
PMID
27528719
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
33
Publish Date
2016
Start Page
4040
End Page
4046
DOI
10.1200/jco.2016.68.3573

Society of Surgical Oncology–American Society for Radiation Oncology–American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Ductal Carcinoma In Situ

Authors
Morrow, M; Van Zee, KJ; Solin, LJ; Houssami, N; Chavez-MacGregor, M; Harris, JR; Horton, J; Hwang, S; Johnson, PL; Marinovich, ML; Schnitt, SJ; Wapnir, I; Moran, MS
MLA Citation
Morrow, M, Van Zee, KJ, Solin, LJ, Houssami, N, Chavez-MacGregor, M, Harris, JR, Horton, J, Hwang, S, Johnson, PL, Marinovich, ML, Schnitt, SJ, Wapnir, I, and Moran, MS. "Society of Surgical Oncology–American Society for Radiation Oncology–American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Ductal Carcinoma In Situ." Annals of Surgical Oncology 23.12 (November 2016): 3801-3810.
Source
crossref
Published In
Annals of Surgical Oncology
Volume
23
Issue
12
Publish Date
2016
Start Page
3801
End Page
3810
DOI
10.1245/s10434-016-5449-z

The Impact of the Affordable Care Act on North Carolinian Breast Cancer Patients Seeking Financial Support for Treatment.

The Affordable Care Act (ACA) was instated on 23 March 2010 to improve healthcare quality, reduce costs, and increase access. The Pretty in Pink Foundation (PIPF), a non-profit 501(C)(3) organization in North Carolina, provides financial assistance and in-kind support to individuals seeking help with breast cancer care. The objective of this study was to determine whether sociodemographic variables and treatment services varied among PIPF recipients since enactment of the ACA.North Carolinians who received financial assistance from the PIPF between 1 January 2013 and 31 December 2014 were included in the study, and the cohort was divided into two groups based on receipt of assistance before or after the enactment of the ACA. Descriptive statistics were tabulated as frequencies. Comparative univariate analysis between both groups was conducted using the χ (2) and Mann-Whitney U tests. All tests were two-sided and a p value <0.05 was considered statistically significant. All analyses were conducted using Stata.Overall, 1016 individuals fulfilled the inclusion criteria, and the median age of the cohort was 49 years (interquartile range 45-55). The ACA groups did not differ significantly by age, race, and sex; however, the groups varied with respect to income, employment, and clinical stage. In addition, the groups differed on the types of services for which they received financial assistance, but no difference was observed between groups with respect to insurance status.Since the enactment of the health insurance market component of the ACA, there has been a reduction in subjects receiving assistance from the PIPF; however, no change in their insurance status has been observed.

Authors
Obeng-Gyasi, S; Tolnitch, L; Greenup, RA; Shelley Hwang, E
MLA Citation
Obeng-Gyasi, S, Tolnitch, L, Greenup, RA, and Shelley Hwang, E. "The Impact of the Affordable Care Act on North Carolinian Breast Cancer Patients Seeking Financial Support for Treatment." Annals of surgical oncology 23.10 (October 2016): 3412-3417.
PMID
27411550
Source
epmc
Published In
Annals of Surgical Oncology
Volume
23
Issue
10
Publish Date
2016
Start Page
3412
End Page
3417
DOI
10.1245/s10434-016-5311-3

Interleukin-10: An Immune-Activating Cytokine in Cancer Immunotherapy.

Authors
Zhang, H; Wang, Y; Hwang, ES; He, Y-W
MLA Citation
Zhang, H, Wang, Y, Hwang, ES, and He, Y-W. "Interleukin-10: An Immune-Activating Cytokine in Cancer Immunotherapy." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.29 (October 2016): 3576-3578.
PMID
27573656
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
29
Publish Date
2016
Start Page
3576
End Page
3578
DOI
10.1200/jco.2016.69.6435

Current Trends in the Management of Ductal Carcinoma In Situ.

Ductal carcinoma in situ (DCIS), once a rare entity, now comprises up to 30% of newly diagnosed breast cancers detected on mammography. It is now appreciated as a widely heterogeneous disease, with indolent lesions of minimal clinical significance on one end of the spectrum, and aggressive lesions with malignant invasive potential on the other. Therefore, the traditional guideline-concordant approach to treatment with surgery, radiation, and endocrine therapy may lead to overtreatment of certain patients, and insufficient treatment of others. Risk assessment using clinical and molecular prognostic tools is being investigated, addressing the possibility of delineating subpopulations that may be treated with more tailored therapy. This review will summarize the current trends in the diagnosis and management of DCIS and will highlight ongoing trials that are shaping future management of this entity.

Authors
Park, TS; Hwang, ES
MLA Citation
Park, TS, and Hwang, ES. "Current Trends in the Management of Ductal Carcinoma In Situ." Oncology (Williston Park, N.Y.) 30.9 (September 2016): 823-831. (Review)
PMID
27633413
Source
epmc
Published In
Oncology
Volume
30
Issue
9
Publish Date
2016
Start Page
823
End Page
831

Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma in Situ.

Controversy exists regarding the optimal negative margin width for ductal carcinoma in situ (DCIS) treated with breast-conserving surgery and whole-breast irradiation.A multidisciplinary consensus panel used a meta-analysis of margin width and ipsilateral breast tumor recurrence (IBTR) from a systematic review of 20 studies including 7883 patients and other published literature as the evidence base for consensus.Negative margins halve the risk of IBTR compared with positive margins defined as ink on DCIS. A 2-mm margin minimizes the risk of IBTR compared with smaller negative margins. More widely clear margins do not significantly decrease IBTR compared with 2-mm margins. Negative margins narrower than 2 mm alone are not an indication for mastectomy, and factors known to affect rates of IBTR should be considered in determining the need for re-excision.Use of a 2-mm margin as the standard for an adequate margin in DCIS treated with whole-breast irradiation is associated with lower rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins narrower than 2 mm.

Authors
Morrow, M; Van Zee, KJ; Solin, LJ; Houssami, N; Chavez-MacGregor, M; Harris, JR; Horton, J; Hwang, S; Johnson, PL; Marinovich, ML; Schnitt, SJ; Wapnir, I; Moran, MS
MLA Citation
Morrow, M, Van Zee, KJ, Solin, LJ, Houssami, N, Chavez-MacGregor, M, Harris, JR, Horton, J, Hwang, S, Johnson, PL, Marinovich, ML, Schnitt, SJ, Wapnir, I, and Moran, MS. "Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma in Situ." Practical radiation oncology 6.5 (September 2016): 287-295.
PMID
27538810
Source
epmc
Published In
Practical Radiation Oncology
Volume
6
Issue
5
Publish Date
2016
Start Page
287
End Page
295
DOI
10.1016/j.prro.2016.06.011

Can Vascular Patterns on Preoperative Magnetic Resonance Imaging Help Predict Skin Necrosis after Nipple-Sparing Mastectomy?

Nipple-areola complex (NAC) and skin flap ischemia and necrosis can occur after nipple-sparing mastectomy (NSM). The purpose of this study was to correlate vascular findings on MRI with outcomes in patients who underwent NSM.Female patients at a single institution who underwent NSM and had a preoperative breast MRI between 2010 and 2014 were identified. Medical records were reviewed for patient demographics, surgical factors, and complications. Magnetic resonance images were reviewed by 2 radiologists, blinded to outcomes, for the presence of dual vs single blood supply to the breast. The association between blood supply on MRI with ischemic and necrotic complications after NSM was analyzed.One hundred and sixty-four NSM procedures were performed in 105 patients (mean age 45.5 years, range 25 to 69 years) who had a preoperative MRI. The majority of procedures were performed for malignancy (89 of 164 [54.3%]) or prophylaxis (73 of 164 [44.5%]). Nipple-areola complex or skin flap ischemia or necrosis occurred in 40 (24.4%) breasts. Ischemia or necrosis after NSM was less likely to occur in breasts with dual compared with single blood supply (20.8% vs 38.2%; p = 0.03). There was no association between surgical complications and age, BMI, smoking history, previous radiation therapy, indication for NSM, surgical specimen weight, surgical incision type, reconstruction approach, or operating surgeon on univariate analysis.Preoperative MRI characterization of breast vascularity can be considered when planning NSM. The presence of a dual blood supply to the breast on MRI is associated with a decreased risk of nipple-areola complex and skin flap ischemia and necrosis after NSM.

Authors
Bahl, M; Pien, IJ; Buretta, KJ; Hwang, ES; Greenup, RA; Ghate, SV; Hollenbeck, ST
MLA Citation
Bahl, M, Pien, IJ, Buretta, KJ, Hwang, ES, Greenup, RA, Ghate, SV, and Hollenbeck, ST. "Can Vascular Patterns on Preoperative Magnetic Resonance Imaging Help Predict Skin Necrosis after Nipple-Sparing Mastectomy?." Journal of the American College of Surgeons 223.2 (August 2016): 279-285.
PMID
27182036
Source
epmc
Published In
Journal of The American College of Surgeons
Volume
223
Issue
2
Publish Date
2016
Start Page
279
End Page
285
DOI
10.1016/j.jamcollsurg.2016.04.045

Reoperation for Margins After Breast Conservation Surgery: What's Old Is New Again.

Authors
Nag, U; Hwang, ES
MLA Citation
Nag, U, and Hwang, ES. "Reoperation for Margins After Breast Conservation Surgery: What's Old Is New Again." JAMA surgery 151.7 (July 2016): 656-.
PMID
26885584
Source
epmc
Published In
JAMA Surgery
Volume
151
Issue
7
Publish Date
2016
Start Page
656
DOI
10.1001/jamasurg.2015.5555

Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013.

The objective of this study was to determine whether the 21-gene Recurrence Score (RS) provides clinically meaningful information in patients with de novo stage IV breast cancer enrolled in the Translational Breast Cancer Research Consortium (TBCRC) 013.TBCRC 013 was a multicenter prospective registry that evaluated the role of surgery of the primary tumor in patients with de novo stage IV breast cancer. From July 2009 to April 2012, 127 patients from 14 sites were enrolled; 109 (86%) patients had pretreatment primary tumor samples suitable for 21-gene RS analysis. Clinical variables, time to first progression (TTP), and 2-year overall survival (OS) were correlated with the 21-gene RS by using log-rank, Kaplan-Meier, and Cox regression.Median patient age was 52 years (21 to 79 years); the majority had hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (72 [66%]) or hormone receptor-positive/HER2-positive (20 [18%]) breast cancer. At a median follow-up of 29 months, median TTP was 20 months (95% CI, 16 to 26 months), and median survival was 49 months (95% CI, 40 months to not reached). An RS was generated for 101 (93%) primary tumor samples: 22 (23%) low risk (< 18), 29 (28%) intermediate risk (18 to 30); and 50 (49%) high risk (≥ 31). For all patients, RS was associated with TTP (P = .01) and 2-year OS (P = .04). In multivariable Cox regression models among 69 patients with estrogen receptor (ER)-positive/HER2-negative cancer, RS was independently prognostic for TTP (hazard ratio, 1.40; 95% CI, 1.05 to 1.86; P = .02) and 2-year OS (hazard ratio, 1.83; 95% CI, 1.14 to 2.95; P = .013).The 21-gene RS is independently prognostic for both TTP and 2-year OS in ER-positive/HER2-negative de novo stage IV breast cancer. Prospective validation is needed to determine the potential role for this assay in the clinical management of this patient subset.

Authors
King, TA; Lyman, JP; Gonen, M; Voci, A; De Brot, M; Boafo, C; Sing, AP; Hwang, ES; Alvarado, MD; Liu, MC; Boughey, JC; McGuire, KP; Van Poznak, CH; Jacobs, LK; Meszoely, IM; Krontiras, H; Babiera, GV; Norton, L; Morrow, M; Hudis, CA
MLA Citation
King, TA, Lyman, JP, Gonen, M, Voci, A, De Brot, M, Boafo, C, Sing, AP, Hwang, ES, Alvarado, MD, Liu, MC, Boughey, JC, McGuire, KP, Van Poznak, CH, Jacobs, LK, Meszoely, IM, Krontiras, H, Babiera, GV, Norton, L, Morrow, M, and Hudis, CA. "Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.20 (July 2016): 2359-2365.
PMID
27001590
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
20
Publish Date
2016
Start Page
2359
End Page
2365
DOI
10.1200/jco.2015.63.1960

Contemporary management of ductal carcinoma in situ and lobular carcinoma in situ.

The management of in situ lesions ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS) continues to evolve. These diagnoses now comprise a large burden of mammographically diagnosed cancers, and with a global trend towards more population-based screening, the incidence of these lesions will continue to rise. Because outcomes following treatment for DCIS and LCIS are excellent, there is emerging controversy about what extent of treatment is optimal for both diseases. Here we review the current approaches to the diagnosis and treatment of both DCIS and LCIS. In addition, we will consider potential directions for future management of these lesions.

Authors
Obeng-Gyasi, S; Ong, C; Hwang, ES
MLA Citation
Obeng-Gyasi, S, Ong, C, and Hwang, ES. "Contemporary management of ductal carcinoma in situ and lobular carcinoma in situ." Chinese clinical oncology 5.3 (June 2016): 32-. (Review)
PMID
27197512
Source
epmc
Published In
Chinese clinical oncology
Volume
5
Issue
3
Publish Date
2016
Start Page
32
DOI
10.21037/cco.2016.04.02

Patient-Reported Outcomes After Choice for Contralateral Prophylactic Mastectomy

Authors
Hwang, ES; Locklear, TD; Rushing, CN; Samsa, G; Abernethy, AP; Hyslop, T; Atisha, DM
MLA Citation
Hwang, ES, Locklear, TD, Rushing, CN, Samsa, G, Abernethy, AP, Hyslop, T, and Atisha, DM. "Patient-Reported Outcomes After Choice for Contralateral Prophylactic Mastectomy." JOURNAL OF CLINICAL ONCOLOGY 34.13 (May 1, 2016): 1518-+.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
34
Issue
13
Publish Date
2016
Start Page
1518
End Page
+
DOI
10.1200/JCO.2015.61.5427

Patient-Reported Outcomes After Choice for Contralateral Prophylactic Mastectomy.

The rate of contralateral prophylactic mastectomies (CPMs) continues to rise, although there is little evidence to support improvement in quality of life (QOL) with CPM. We sought to ascertain whether patient-reported outcomes and, more specifically, QOL differed according to receipt of CPM.Volunteers recruited from the Army of Women with a history of breast cancer surgery took an electronically administered survey, which included the BREAST-Q, a well-validated breast surgery outcomes patient-reporting tool, and demographic and treatment-related questions. Descriptive statistics, hypothesis testing, and regression analysis were used to evaluate the association of CPM with four BREAST-Q QOL domains.A total of 7,619 women completed questionnaires; of those eligible, 3,977 had a mastectomy and 1,598 reported receipt of CPM. Women undergoing CPM were younger than those who did not choose CPM. On unadjusted analysis, mean breast satisfaction was higher in the CPM group (60.4 v 57.9, P < .001) and mean physical well-being was lower in the CPM group (74.6 v 76.6, P < .001). On multivariable analysis, the CPM group continued to report higher breast satisfaction (P = .046) and psychosocial well-being (P = .017), but no difference was reported in the no-CPM group in the other QOL domains.Choice for CPM was associated with an improvement in breast satisfaction and psychosocial well-being. However, the magnitude of the effect may be too small to be clinically meaningful. Such patient-reported outcomes data are important to consider when counseling women contemplating CPM as part of their breast cancer treatment.

Authors
Hwang, ES; Locklear, TD; Rushing, CN; Samsa, G; Abernethy, AP; Hyslop, T; Atisha, DM
MLA Citation
Hwang, ES, Locklear, TD, Rushing, CN, Samsa, G, Abernethy, AP, Hyslop, T, and Atisha, DM. "Patient-Reported Outcomes After Choice for Contralateral Prophylactic Mastectomy." May 2016.
PMID
26951322
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
13
Publish Date
2016
Start Page
1518
End Page
1527
DOI
10.1200/jco.2015.61.5427

Outcomes of Active Surveillance for Ductal Carcinoma in Situ: A Computational Risk Analysis.

Ductal carcinoma in situ (DCIS) is a noninvasive breast lesion with uncertain risk for invasive progression. Usual care (UC) for DCIS consists of treatment upon diagnosis, thus potentially overtreating patients with low propensity for progression. One strategy to reduce overtreatment is active surveillance (AS), whereby DCIS is treated only upon detection of invasive disease. Our goal was to perform a quantitative evaluation of outcomes following an AS strategy for DCIS.Age-stratified, 10-year disease-specific cumulative mortality (DSCM) for AS was calculated using a computational risk projection model based upon published estimates for natural history parameters, and Surveillance, Epidemiology, and End Results data for outcomes. AS projections were compared with the DSCM for patients who received UC. To quantify the propagation of parameter uncertainty, a 95% projection range (PR) was computed, and sensitivity analyses were performed.Under the assumption that AS cannot outperform UC, the projected median differences in 10-year DSCM between AS and UC when diagnosed at ages 40, 55, and 70 years were 2.6% (PR = 1.4%-5.1%), 1.5% (PR = 0.5%-3.5%), and 0.6% (PR = 0.0%-2.4), respectively. Corresponding median numbers of patients needed to treat to avert one breast cancer death were 38.3 (PR = 19.7-69.9), 67.3 (PR = 28.7-211.4), and 157.2 (PR = 41.1-3872.8), respectively. Sensitivity analyses showed that the parameter with greatest impact on DSCM was the probability of understaging invasive cancer at diagnosis.AS could be a viable management strategy for carefully selected DCIS patients, particularly among older age groups and those with substantial competing mortality risks. The effectiveness of AS could be markedly improved by reducing the rate of understaging.

Authors
Ryser, MD; Worni, M; Turner, EL; Marks, JR; Durrett, R; Hwang, ES
MLA Citation
Ryser, MD, Worni, M, Turner, EL, Marks, JR, Durrett, R, and Hwang, ES. "Outcomes of Active Surveillance for Ductal Carcinoma in Situ: A Computational Risk Analysis." Journal of the National Cancer Institute 108.5 (May 2016).
PMID
26683405
Source
epmc
Published In
Journal of the National Cancer Institute
Volume
108
Issue
5
Publish Date
2016
DOI
10.1093/jnci/djv372

Imaging-Guided Core-Needle Breast Biopsy: Impact of Meditation and Music Interventions on Patient Anxiety, Pain, and Fatigue.

To evaluate the impact of guided meditation and music interventions on patient anxiety, pain, and fatigue during imaging-guided breast biopsy.After giving informed consent, 121 women needing percutaneous imaging-guided breast biopsy were randomized into three groups: (1) guided meditation; (2) music; (3) standard-care control group. During biopsy, the meditation and music groups listened to an audio-recorded, guided, loving-kindness meditation and relaxing music, respectively; the standard-care control group received supportive dialogue from the biopsy team. Immediately before and after biopsy, participants completed questionnaires measuring anxiety (State-Trait Anxiety Inventory Scale), biopsy pain (Brief Pain Inventory), and fatigue (modified Functional Assessment of Chronic Illness Therapy-Fatigue). After biopsy, participants completed questionnaires assessing radiologist-patient communication (modified Questionnaire on the Quality of Physician-Patient Interaction), demographics, and medical history.The meditation and music groups reported significantly greater anxiety reduction (P values < .05) and reduced fatigue after biopsy than the standard-care control group; the standard-care control group reported increased fatigue after biopsy. The meditation group additionally showed significantly lower pain during biopsy, compared with the music group (P = .03). No significant difference in patient-perceived quality of radiologist-patient communication was noted among groups.Listening to guided meditation significantly lowered biopsy pain during imaging-guided breast biopsy; meditation and music reduced patient anxiety and fatigue without compromising radiologist-patient communication. These simple, inexpensive interventions could improve women's experiences during core-needle breast biopsy.

Authors
Soo, MS; Jarosz, JA; Wren, AA; Soo, AE; Mowery, YM; Johnson, KS; Yoon, SC; Kim, C; Hwang, ES; Keefe, FJ; Shelby, RA
MLA Citation
Soo, MS, Jarosz, JA, Wren, AA, Soo, AE, Mowery, YM, Johnson, KS, Yoon, SC, Kim, C, Hwang, ES, Keefe, FJ, and Shelby, RA. "Imaging-Guided Core-Needle Breast Biopsy: Impact of Meditation and Music Interventions on Patient Anxiety, Pain, and Fatigue." Journal of the American College of Radiology : JACR 13.5 (May 2016): 526-534.
PMID
26853501
Source
epmc
Published In
Journal of the American College of Radiology
Volume
13
Issue
5
Publish Date
2016
Start Page
526
End Page
534
DOI
10.1016/j.jacr.2015.12.004

Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In-situ in Patients with Lobular Neoplasia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 020).

Lobular neoplasia (LN) represents a spectrum of atypical proliferative lesions, including atypical lobular hyperplasia and lobular carcinoma-in-situ. The need for excision for LN found on core biopsy (CB) is controversial. We conducted a prospective multi-institutional trial (TBCRC 20) to determine the rate of upgrade to cancer after excision for pure LN on CB.Patients with a CB diagnosis of pure LN were prospectively identified and consented to excision. Cases with discordant imaging and those with additional lesions requiring excision were excluded. Upgrade rates to cancer were quantified on the basis of local and central pathology review. Confidence intervals and sample size were based on exact binomial calculations.A total of 77 of 79 registered patients underwent excision (median age 51 years, range 27-82 years). Two cases (3%; 95% confidence interval 0.3-9) were upgraded to cancer (one tubular carcinoma, one ductal carcinoma-in-situ) at excision per local pathology. Central pathology review of 76 cases confirmed pure LN in the CB in all but two cases. In one case, the tubular carcinoma identified at excision was also found in the CB specimen, and in the other, LN was not identified, yielding an upgrade rate of one case (1%; 95% CI 0.01-7) by central pathology review.In this prospective study of 77 patients with pure LN on CB, the upgrade rate was 3% by local pathology and 1% by central pathology review, demonstrating that routine excision is not indicated for patients with pure LN on CB and concordant imaging findings.

Authors
Nakhlis, F; Gilmore, L; Gelman, R; Bedrosian, I; Ludwig, K; Hwang, ES; Willey, S; Hudis, C; Iglehart, JD; Lawler, E; Ryabin, NY; Golshan, M; Schnitt, SJ; King, TA
MLA Citation
Nakhlis, F, Gilmore, L, Gelman, R, Bedrosian, I, Ludwig, K, Hwang, ES, Willey, S, Hudis, C, Iglehart, JD, Lawler, E, Ryabin, NY, Golshan, M, Schnitt, SJ, and King, TA. "Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In-situ in Patients with Lobular Neoplasia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 020)." Annals of surgical oncology 23.3 (March 2016): 722-728.
PMID
26542585
Source
epmc
Published In
Annals of Surgical Oncology
Volume
23
Issue
3
Publish Date
2016
Start Page
722
End Page
728
DOI
10.1245/s10434-015-4922-4

Abstract P5-17-03: The 12-gene DCIS score assay: Impact on radiation treatment (XRT) recommendations and clinical utility

Authors
Manders, JB; Kuerer, HM; Smith, BD; McCluskey, C; Farrar, WB; Frazier, TG; Li, L; Leonard, CE; Carter, DL; Chawla, S; Medeiros, LE; Guenther, JM; Castellini, LE; Buchholz, DJ; Mamounas, EP; Wapnir, IL; Horst, KC; Chagpar, A; Evans, SB; Riker, AI; Vali, FS; Solin, LJ; Jablon, L; Recht, A; Sharma, R; Lu, R; Sing, AP; Hwang, ES; White, J
MLA Citation
Manders, JB, Kuerer, HM, Smith, BD, McCluskey, C, Farrar, WB, Frazier, TG, Li, L, Leonard, CE, Carter, DL, Chawla, S, Medeiros, LE, Guenther, JM, Castellini, LE, Buchholz, DJ, Mamounas, EP, Wapnir, IL, Horst, KC, Chagpar, A, Evans, SB, Riker, AI, Vali, FS, Solin, LJ, Jablon, L, Recht, A, Sharma, R, Lu, R, Sing, AP, Hwang, ES, and White, J. "Abstract P5-17-03: The 12-gene DCIS score assay: Impact on radiation treatment (XRT) recommendations and clinical utility." February 15, 2016.
Source
crossref
Published In
Cancer Research
Volume
76
Issue
4 Supplement
Publish Date
2016
Start Page
P5-17-03
End Page
P5-17-03
DOI
10.1158/1538-7445.SABCS15-P5-17-03

Abstract ES8-3: Endocrine management of premalignant lesions and DCIS

Authors
Hwang, ES
MLA Citation
Hwang, ES. "Abstract ES8-3: Endocrine management of premalignant lesions and DCIS." February 15, 2016.
Source
crossref
Published In
Cancer Research
Volume
76
Issue
4 Supplement
Publish Date
2016
Start Page
ES8-3
End Page
ES8-3
DOI
10.1158/1538-7445.SABCS15-ES8-3

National Practice Patterns Among Women with Stage IV Breast Cancer Undergoing Surgery at the Primary Site

Authors
Lane, WO; Houck, K; Hwang, ES; Greenup, R
MLA Citation
Lane, WO, Houck, K, Hwang, ES, and Greenup, R. "National Practice Patterns Among Women with Stage IV Breast Cancer Undergoing Surgery at the Primary Site." February 2016.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
23
Publish Date
2016
Start Page
S73
End Page
S73

Implementation of the Distress Thermometer Among Surgical Breast Cancer Patients at a Comprehensive Breast Center

Authors
Obeng-Gyasi, S; Stashko, I; Power, S; Marcom, PK; Hwang, ES
MLA Citation
Obeng-Gyasi, S, Stashko, I, Power, S, Marcom, PK, and Hwang, ES. "Implementation of the Distress Thermometer Among Surgical Breast Cancer Patients at a Comprehensive Breast Center." February 2016.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
23
Publish Date
2016
Start Page
S71
End Page
S71

A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer.

Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial. In mice, intravenous injection of LUM015 labeled tumor cells, and residual fluorescence within the tumor bed predicted local recurrence. In 15 patients with STS or breast cancer, intravenous injection of LUM015 before surgery was well tolerated. Imaging of resected human tissues showed that fluorescence from tumor was significantly higher than fluorescence from normal tissues. LUM015 biodistribution, pharmacokinetic profiles, and metabolism were similar in mouse and human subjects. Tissue concentrations of LUM015 and its metabolites, including fluorescently labeled lysine, demonstrated that LUM015 is selectively distributed to tumors where it is activated by proteases. Experiments in mice with a constitutively active PEGylated fluorescent imaging probe support a model where tumor-selective probe distribution is a determinant of increased fluorescence in cancer. These co-clinical studies suggest that the tumor specificity of protease-activated imaging probes, such as LUM015, is dependent on both biodistribution and enzyme activity. Our first-in-human data support future clinical trials of LUM015 and other protease-sensitive probes.

Authors
Whitley, MJ; Cardona, DM; Lazarides, AL; Spasojevic, I; Ferrer, JM; Cahill, J; Lee, C-L; Snuderl, M; Blazer, DG; Hwang, ES; Greenup, RA; Mosca, PJ; Mito, JK; Cuneo, KC; Larrier, NA; O'Reilly, EK; Riedel, RF; Eward, WC; Strasfeld, DB; Fukumura, D; Jain, RK; Lee, WD; Griffith, LG; Bawendi, MG; Kirsch, DG; Brigman, BE
MLA Citation
Whitley, MJ, Cardona, DM, Lazarides, AL, Spasojevic, I, Ferrer, JM, Cahill, J, Lee, C-L, Snuderl, M, Blazer, DG, Hwang, ES, Greenup, RA, Mosca, PJ, Mito, JK, Cuneo, KC, Larrier, NA, O'Reilly, EK, Riedel, RF, Eward, WC, Strasfeld, DB, Fukumura, D, Jain, RK, Lee, WD, Griffith, LG, Bawendi, MG, Kirsch, DG, and Brigman, BE. "A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer." Science translational medicine 8.320 (January 2016): 320ra4-.
PMID
26738797
Source
epmc
Published In
Science Translational Medicine
Volume
8
Issue
320
Publish Date
2016
Start Page
320ra4
DOI
10.1126/scitranslmed.aad0293

DNA defects, epigenetics, and gene expression in cancer-adjacent breast: a study from The Cancer Genome Atlas.

Recurrence rates after breast-conserving therapy may depend on genomic characteristics of cancer-adjacent, benign-appearing tissue. Studies have not evaluated recurrence in association with multiple genomic characteristics of cancer-adjacent breast tissue. To estimate the prevalence of DNA defects and RNA expression subtypes in cancer-adjacent, benign-appearing breast tissue at least 2 cm from the tumor margin, cancer-adjacent, pathologically well-characterized, benign-appearing breast tissue specimens from The Cancer Genome Atlas project were analyzed for DNA sequence, copy-number variation, DNA methylation, messenger RNA (mRNA) sequence, and mRNA/microRNA expression. Additional samples were also analyzed by at least one of these genomic data types and associations between genomic characteristics of normal tissue and overall survival were assessed. Approximately 40% of cancer-adjacent, benign-appearing tissues harbored genomic defects in DNA copy number, sequence, methylation, or in RNA sequence, although these defects did not significantly predict 10-year overall survival. Two mRNA/microRNA expression phenotypes were observed, including an active mRNA subtype that was identified in 40% of samples. Controlling for tumor characteristics and the presence of genomic defects, this active subtype was associated with significantly worse 10-year survival among estrogen receptor (ER)-positive cases. This multi-platform analysis of breast cancer-adjacent samples produced genomic findings consistent with current surgical margin guidelines, and provides evidence that extratumoral RNA expression patterns in cancer-adjacent tissue predict overall survival among patients with ER-positive disease.

Authors
Troester, MA; Hoadley, KA; D'Arcy, M; Cherniack, AD; Stewart, C; Koboldt, DC; Robertson, AG; Mahurkar, S; Shen, H; Wilkerson, MD; Sandhu, R; Johnson, NB; Allison, KH; Beck, AH; Yau, C; Bowen, J; Sheth, M; Hwang, ES; Perou, CM; Laird, PW; Ding, L; Benz, CC
MLA Citation
Troester, MA, Hoadley, KA, D'Arcy, M, Cherniack, AD, Stewart, C, Koboldt, DC, Robertson, AG, Mahurkar, S, Shen, H, Wilkerson, MD, Sandhu, R, Johnson, NB, Allison, KH, Beck, AH, Yau, C, Bowen, J, Sheth, M, Hwang, ES, Perou, CM, Laird, PW, Ding, L, and Benz, CC. "DNA defects, epigenetics, and gene expression in cancer-adjacent breast: a study from The Cancer Genome Atlas." NPJ Breast Cancer 2 (January 2016): 16007-.
PMID
28721375
Source
epmc
Published In
npj Breast Cancer
Volume
2
Publish Date
2016
Start Page
16007
DOI
10.1038/npjbcancer.2016.7

Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In Situ.

Impact of contemporary treatment of pre-invasive breast cancer (ductal carcinoma in situ [DCIS]) on long-term outcomes remains poorly defined. We aimed to evaluate national treatment trends for DCIS and to determine their impact on disease-specific (DSS) and overall survival (OS).The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients diagnosed with DCIS from 1991 to 2010. Treatment pattern trends were analyzed using Cochran-Armitage trend test. Survival analyses were performed using inverse probability weights (IPW)-adjusted competing risk analyses for DSS and Cox proportional hazard regression for OS. All tests performed were two-sided.One hundred twenty-one thousand and eighty DCIS patients were identified. The greatest proportion of patients was treated with lumpectomy and radiation therapy (43.0%), followed by lumpectomy alone (26.5%) and unilateral (23.8%) or bilateral mastectomy (4.5%) with significant shifts over time. The rate of sentinel lymph node biopsy increased from 9.7% to 67.1% for mastectomy and from 1.4% to 17.8% for lumpectomy. Compared with mastectomy, OS was higher for lumpectomy with radiation (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.76 to 0.83, P < .001) and lower for lumpectomy alone (HR = 1.17, 95% CI = 1.13 to 1.23, P < .001). IPW-adjusted ten-year DSS was highest in lumpectomy with XRT (98.9%), followed by mastectomy (98.5%), and lumpectomy alone (98.4%).We identified substantial shifts in treatment patterns for DCIS from 1991 to 2010. When outcomes between locoregional treatment options were compared, we observed greater differences in OS than DSS, likely reflecting both a prevailing patient selection bias as well as clinically negligible differences in breast cancer outcomes between groups.

Authors
Worni, M; Akushevich, I; Greenup, R; Sarma, D; Ryser, MD; Myers, ER; Hwang, ES
MLA Citation
Worni, M, Akushevich, I, Greenup, R, Sarma, D, Ryser, MD, Myers, ER, and Hwang, ES. "Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In Situ." Journal of the National Cancer Institute 107.12 (December 2015): djv263-.
PMID
26424776
Source
epmc
Published In
Journal of the National Cancer Institute
Volume
107
Issue
12
Publish Date
2015
Start Page
djv263
DOI
10.1093/jnci/djv263

Preoperative Partial Breast Radiation Therapy: Short-term Imaging Outcomes With Two Unique Treatment Regimens

Authors
Horton, JK; Baker, JA; Blitzblau, R; Georgiade, GS; Hwang, ES; Duffy, EA; Morgan, M; Feigenberg, SJ; Citron, W; Kesmodel, S; Bellavance, E; Drogula, C; Tkaczuk, K; Galandak, J; Nichols, EM
MLA Citation
Horton, JK, Baker, JA, Blitzblau, R, Georgiade, GS, Hwang, ES, Duffy, EA, Morgan, M, Feigenberg, SJ, Citron, W, Kesmodel, S, Bellavance, E, Drogula, C, Tkaczuk, K, Galandak, J, and Nichols, EM. "Preoperative Partial Breast Radiation Therapy: Short-term Imaging Outcomes With Two Unique Treatment Regimens." November 1, 2015.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
E46
End Page
E46

Preoperative External Beam APBI: Report of Acute Toxicities From 2 Prospective Clinical Trials Using Two Different Fractionation Schemes

Authors
Nichols, E; Feigenberg, SJ; Morgan, M; Citron, W; Kesmodel, S; Bellavance, E; Drogula, C; Tkaczuk, KH; Rosenblatt, P; Georgiade, GS; Hwang, ES; Broadwater, G; Duffy, EA; Blitzblau, R; Horton, JK
MLA Citation
Nichols, E, Feigenberg, SJ, Morgan, M, Citron, W, Kesmodel, S, Bellavance, E, Drogula, C, Tkaczuk, KH, Rosenblatt, P, Georgiade, GS, Hwang, ES, Broadwater, G, Duffy, EA, Blitzblau, R, and Horton, JK. "Preoperative External Beam APBI: Report of Acute Toxicities From 2 Prospective Clinical Trials Using Two Different Fractionation Schemes." November 1, 2015.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
93
Issue
3
Publish Date
2015
Start Page
E49
End Page
E49

Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration.

Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta.

Authors
Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, YY; Liphardt, J; Hwang, ES; Weaver, VM
MLA Citation
Acerbi, I, Cassereau, L, Dean, I, Shi, Q, Au, A, Park, C, Chen, YY, Liphardt, J, Hwang, ES, and Weaver, VM. "Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration." Integrative biology : quantitative biosciences from nano to macro 7.10 (October 2015): 1120-1134.
PMID
25959051
Source
epmc
Published In
Integrative Biology
Volume
7
Issue
10
Publish Date
2015
Start Page
1120
End Page
1134
DOI
10.1039/c5ib00040h

Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

Authors
Ciriello, G; Gatza, ML; Beck, AH; Wilkerson, MD; Rhie, SK; Pastore, A; Zhang, H; McLellan, M; Yau, C; Kandoth, C; Bowlby, R; Shen, H; Hayat, S; Fieldhouse, R; Lester, SC; Tse, GMK; Factor, RE; Collins, LC; Allison, KH; Chen, Y-Y; Jensen, K; Johnson, NB; Oesterreich, S; Mills, GB; Cherniack, AD; Robertson, G; Benz, C; Sander, C; Laird, PW; Hoadley, KA; King, TA; TCGA Research Network, ; Perou, CM
MLA Citation
Ciriello, G, Gatza, ML, Beck, AH, Wilkerson, MD, Rhie, SK, Pastore, A, Zhang, H, McLellan, M, Yau, C, Kandoth, C, Bowlby, R, Shen, H, Hayat, S, Fieldhouse, R, Lester, SC, Tse, GMK, Factor, RE, Collins, LC, Allison, KH, Chen, Y-Y, Jensen, K, Johnson, NB, Oesterreich, S, Mills, GB, Cherniack, AD, Robertson, G, Benz, C, Sander, C, Laird, PW, Hoadley, KA, King, TA, TCGA Research Network, , and Perou, CM. "Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer." Cell 163.2 (October 2015): 506-519.
PMID
26451490
Source
epmc
Published In
Cell
Volume
163
Issue
2
Publish Date
2015
Start Page
506
End Page
519
DOI
10.1016/j.cell.2015.09.033

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers.

Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response.Women aged ≥55 years with clinically node-negative, estrogen receptor-positive, and/or progesterone receptor-positive HER2-, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed.No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation.Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should be tested in future clinical trials because it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.

Authors
Horton, JK; Blitzblau, RC; Yoo, S; Geradts, J; Chang, Z; Baker, JA; Georgiade, GS; Chen, W; Siamakpour-Reihani, S; Wang, C; Broadwater, G; Groth, J; Palta, M; Dewhirst, M; Barry, WT; Duffy, EA; Chi, J-TA; Hwang, ES
MLA Citation
Horton, JK, Blitzblau, RC, Yoo, S, Geradts, J, Chang, Z, Baker, JA, Georgiade, GS, Chen, W, Siamakpour-Reihani, S, Wang, C, Broadwater, G, Groth, J, Palta, M, Dewhirst, M, Barry, WT, Duffy, EA, Chi, J-TA, and Hwang, ES. "Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers." International journal of radiation oncology, biology, physics 92.4 (July 2015): 846-855.
PMID
26104938
Source
epmc
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
92
Issue
4
Publish Date
2015
Start Page
846
End Page
855
DOI
10.1016/j.ijrobp.2015.03.007

Impact of delayed lymphoscintigraphy for sentinel lymphnode biopsy for breast cancer.

BACKGROUND: Despite universal adoption of sentinel lymph node biopsy (SLNB) for breast cancer, there remains no standardized protocol for preoperative lymphoscintographic assessment of sentinel nodes. Both immediate and delayed lymphoscintigraphy are currently utilized, although it is unclear how delayed imaging impacts SLN identification. METHODS: Among patients diagnosed with breast cancer who underwent SLNB at Duke from 2011 to 2012, two protocols for preoperative lymphoscintigraphy were used: protocol A included both immediate and delayed lymphoscintigraphy (n = 152), while protocol B involved immediate lymphoscintigraphy only (n = 103). RESULTS: The overall intraoperative SLN identification rate was 98.4% and did not differ between groups. A lower number of SLN were visualized on the immediate scan using protocol A compared to protocol B (P < 0.001). Although a greater total number of nodes was excised using protocol A, this result was not statistically significant (P = 0.08). Moreover, there was no significant difference in the number of negative SLN between groups (P = 0.51). CONCLUSIONS: We found no significant impact on identification rate or number of SLN excised with the use of delayed versus immediate imaging. These findings support abandoning delayed lymphoscintographic imaging, except in those cases where aberrant drainage is suspected.

Authors
Wang, H; Heck, K; Pruitt, SK; Wong, TZ; Scheri, RP; Georgiade, GS; Ichite, I; Hwang, ES
MLA Citation
Wang, H, Heck, K, Pruitt, SK, Wong, TZ, Scheri, RP, Georgiade, GS, Ichite, I, and Hwang, ES. "Impact of delayed lymphoscintigraphy for sentinel lymphnode biopsy for breast cancer." Journal of surgical oncology 111.8 (June 2015): 931-934.
PMID
25953313
Source
epmc
Published In
Journal of Surgical Oncology
Volume
111
Issue
8
Publish Date
2015
Start Page
931
End Page
934
DOI
10.1002/jso.23915

Abstract P1-10-02: Adjuvant radiation after lumpectomy: A cost comparison of treatment patterns in 43,247 women from the National Cancer Data Base

Authors
Greenup, RA; Blitzblau, R; Houck, K; Horton, J; Howie, L; Palta, M; Mackey, A; Scheri, R; Sosa, JA; Taghian, AG; Peppercorn, J; Smith, BL; Hwang, ES
MLA Citation
Greenup, RA, Blitzblau, R, Houck, K, Horton, J, Howie, L, Palta, M, Mackey, A, Scheri, R, Sosa, JA, Taghian, AG, Peppercorn, J, Smith, BL, and Hwang, ES. "Abstract P1-10-02: Adjuvant radiation after lumpectomy: A cost comparison of treatment patterns in 43,247 women from the National Cancer Data Base." May 1, 2015.
Source
crossref
Published In
Cancer Research
Volume
75
Issue
9 Supplement
Publish Date
2015
Start Page
P1-10-02
End Page
P1-10-02
DOI
10.1158/1538-7445.SABCS14-P1-10-02

Abstract P3-07-22: Predictors of neoadjuvant chemotherapy use in women with breast cancer: A review of 169,329 patients from the American College of Surgeons' National Cancer Database

Authors
Howie, LJ; Greenup, R; Houck, K; Sosa, JA; Hwang, ES; Peppercorn, JM
MLA Citation
Howie, LJ, Greenup, R, Houck, K, Sosa, JA, Hwang, ES, and Peppercorn, JM. "Abstract P3-07-22: Predictors of neoadjuvant chemotherapy use in women with breast cancer: A review of 169,329 patients from the American College of Surgeons' National Cancer Database." May 1, 2015.
Source
crossref
Published In
Cancer Research
Volume
75
Issue
9 Supplement
Publish Date
2015
Start Page
P3-07-22
End Page
P3-07-22
DOI
10.1158/1538-7445.SABCS14-P3-07-22

Implications of HER2-targeted therapy on extent of surgery for early-stage breast cancer.

Authors
Aziz, H; Marcom, PK; Hwang, ES
MLA Citation
Aziz, H, Marcom, PK, and Hwang, ES. "Implications of HER2-targeted therapy on extent of surgery for early-stage breast cancer." Annals of surgical oncology 22.5 (May 2015): 1404-1405.
PMID
25777094
Source
epmc
Published In
Annals of Surgical Oncology
Volume
22
Issue
5
Publish Date
2015
Start Page
1404
End Page
1405
DOI
10.1245/s10434-015-4503-6

A national snapshot of satisfaction with breast cancer procedures.

PURPOSE: Women with early-stage breast cancer face the complex decision to undergo one of three equally effective oncologic surgical strategies: breast-conservation surgery with radiation (BCS), mastectomy, or mastectomy with breast reconstruction. With comparable oncologic outcomes and survival rates, evaluations of satisfaction with these procedures are needed to facilitate the decision-making process and to optimize long-term health. METHODS: Women recruited from the Army of Women with a history of breast cancer surgery took electronically administered surgery-specific surveys, including the BREAST-Q© and a background survey evaluating patient-, disease-, and procedure-specific factors. Descriptive statistics and regression analysis were used to evaluate the effect of procedure type on breast satisfaction scores. RESULTS: Overall, 7,619 women completed the questionnaires. Linear regression revealed that women who underwent abdominal flap, or buttock or thigh flap reconstruction reported the highest breast satisfaction score, scoring an average of 5.6 points and 14.4 points higher than BCS, respectively (p < 0.0001 and p = 0.027, respectively). No difference in satisfaction was observed in women who underwent latissimus dorsi flap reconstruction compared with those who underwent BCS. Women who underwent implant reconstruction reported scores 8.6 points lower than BCS (p < 0.0001). Those with mastectomies without reconstruction or complex surgical histories scored, on average, 10 points lower than BCS (p < 0.0001). CONCLUSION: Women who underwent autologous tissue reconstruction reported the highest breast satisfaction, while women undergoing mastectomy without reconstruction reported the lowest satisfaction. These findings emphasize the value of patient-reported outcome measures as an important guide to decision making in breast surgery and underscore the importance of multidisciplinary participation early in the surgical decision-making process.

Authors
Atisha, DM; Rushing, CN; Samsa, GP; Locklear, TD; Cox, CE; Shelley Hwang, E; Zenn, MR; Pusic, AL; Abernethy, AP
MLA Citation
Atisha, DM, Rushing, CN, Samsa, GP, Locklear, TD, Cox, CE, Shelley Hwang, E, Zenn, MR, Pusic, AL, and Abernethy, AP. "A national snapshot of satisfaction with breast cancer procedures." February 2015.
PMID
25465378
Source
epmc
Published In
Annals of Surgical Oncology
Volume
22
Issue
2
Publish Date
2015
Start Page
361
End Page
369
DOI
10.1245/s10434-014-4246-9

Practice patterns in the delivery of radiation therapy after mastectomy among the University of California Athena Breast Health Network.

BACKGROUND: Practice patterns vary with the planning and delivery of PMRT. In our investigation we examined practice patterns in the use of chest wall bolus and a boost among the Athena Breast Health Network (Athena). MATERIALS AND METHODS: Athena is a collaboration among the 5 University of California Medical Centers that aims to integrate clinical care and research. From February 2011 to June 2011, all physicians specializing in the multidisciplinary treatment of breast cancer were invited to take a Web-based practice patterns survey. Sixty-two of the 239 questions focused on radiation therapy practice environment, decision-making processes, and treatment management, including the use of a bolus or boost in PMRT. RESULTS: Ninety-two percent of the radiation oncologists specializing in breast cancer completed the survey. All of the responders use a material to increase the surface dose to the chest wall during PMRT. Materials used included brass mesh, commercial bolus, and custom-designed wax bolus. Fifty percent used tissue equivalent superflab bolus. Fifty-five percent of the respondents routinely use a boost to the chest wall in PMRT. Eighteen percent give a boost depending on the margin status, and 3 of 11 (27%) do not use a boost. CONCLUSION: Our investigation documents practice pattern variation for the use of a PMRT boost and the use of chest wall bolus among the University of California breast cancer radiation oncologists. Further understanding of the practice pattern variation will help guide clinicians in our cancer centers to a more uniform approach in the delivery of PMRT.

Authors
Mayadev, J; Einck, J; Elson, S; Rugo, H; Hwang, S; Bold, R; Daroui, P; McCloskey, S; Yashar, C; Kim, D; Fowble, B
MLA Citation
Mayadev, J, Einck, J, Elson, S, Rugo, H, Hwang, S, Bold, R, Daroui, P, McCloskey, S, Yashar, C, Kim, D, and Fowble, B. "Practice patterns in the delivery of radiation therapy after mastectomy among the University of California Athena Breast Health Network." Clinical breast cancer 15.1 (February 2015): 43-47.
PMID
25245425
Source
epmc
Published In
Clinical Breast Cancer
Volume
15
Issue
1
Publish Date
2015
Start Page
43
End Page
47
DOI
10.1016/j.clbc.2014.07.005

Monitoring and surveillance following DCIS treatment

© Springer Science+Business Media New York 2015. Currently, more than 20% of breast cancers diagnosed in the USA are ductal carcinoma in situ (DCIS; Brinton et al., J Natl Cancer Inst 100:1643-1648, 2008; DeSantis et al., CA Cancer J Clin 64:52-62, 2014; Ernster et al., J Natl Cancer Inst 94:1546-1554, 2002). Early detection and a low breast-cancer-specific mortality (1-2%; Ernster et al., Arch Intern Med 160:953-958, 2000) have resulted in an increasing number of patients that require clinical follow-up and imaging surveillance after treatment for DCIS. As this population continues to grow, clinical evaluation and management patterns are also evolving, including advances in breast imaging, surgery with or without reconstruction, radiation therapy, and systemic therapies. Clinicians must determine long-term follow-up for patients that have taken a variety of pathways to survivorship. As treatment patterns become more individualized for tumor biology and patient preference, surveillance practices must also evolve and be tailored appropriately for survivorship programs. In this chapter, we review the current guidelines for surveillance after treatment for DCIS and discuss a practical application of these guidelines for a spectrum of DCIS survivors.

Authors
Zakhireh, JL; Shelley Hwang, E
MLA Citation
Zakhireh, JL, and Shelley Hwang, E. "Monitoring and surveillance following DCIS treatment." (January 1, 2015): 139-146. (Chapter)
Source
scopus
Publish Date
2015
Start Page
139
End Page
146
DOI
10.1007/978-1-4939-2035-8_14

Surgical patterns of care in patients with invasive breast cancer treated with neoadjuvant systemic therapy and breast magnetic resonance imaging: results of a secondary analysis of TBCRC 017.

Neoadjuvant chemotherapy (NCT) downstages advanced primary tumors, with magnetic resonance imaging (MRI) being the most sensitive imaging predictor of response. However, the impact of MRI evaluation on surgical treatment decisions in the neoadjuvant setting has not been well described. We report surgical patterns of care across 8 National Cancer Institute comprehensive cancer centers in women receiving both NCT and MRI to evaluate the impact of MRI findings on surgical planning.Seven hundred seventy women from 8 institutions received NCT with MRI obtained both before and after systemic treatment. Univariate and multivariate analyses of imaging, patient-, and tumor-related covariates associated with choice of breast surgery were conducted.MRI and surgical data were available on 759 of 770 patients. A total of 345 of 759 (45 %) patients received breast-conserving surgery and 414 of 759 (55 %) received mastectomy. Mastectomy occurred more commonly in patients with incomplete MRI response versus complete (58 vs. 43 %) (p = 0.0003). On multivariate analysis, positive estrogen receptor status (p = 0.02), incomplete MRI response (p = 0.0003), higher baseline T classification (p < 0.0001), younger age (p < 0.0006), and institution (p = 0.003) were independent predictors of mastectomy. A statistically significant trend toward increasing use of mastectomy with increasing T stage at presentation (p < 0.0001) was observed in patients with incomplete response by MRI only. Among women with complete response on MRI, 43 % underwent mastectomy.Within a multi-institutional cohort of women undergoing neoadjuvant treatment for breast cancer, MRI findings were not clearly associated with extent of surgery. This study shows that receptor status, T stage at diagnosis, young age, and treating institution are more significant determinants of surgical treatment choice than MRI response data.

Authors
McGuire, KP; Hwang, ES; Cantor, A; Golshan, M; Meric-Bernstam, F; Horton, JK; Nanda, R; Amos, KD; Forero, A; Hudis, CA; Meszoely, I; De Los Santos, JF
MLA Citation
McGuire, KP, Hwang, ES, Cantor, A, Golshan, M, Meric-Bernstam, F, Horton, JK, Nanda, R, Amos, KD, Forero, A, Hudis, CA, Meszoely, I, and De Los Santos, JF. "Surgical patterns of care in patients with invasive breast cancer treated with neoadjuvant systemic therapy and breast magnetic resonance imaging: results of a secondary analysis of TBCRC 017." Annals of surgical oncology 22.1 (January 2015): 75-81.
PMID
25059792
Source
epmc
Published In
Annals of Surgical Oncology
Volume
22
Issue
1
Publish Date
2015
Start Page
75
End Page
81
DOI
10.1245/s10434-014-3948-3

Lobular breast cancer series: imaging.

The limitations of mammography in the detection and evaluation of invasive lobular carcinoma (ILC) have long been recognized, presenting real clinical challenges in treatment planning for these tumors. However, advances in mammography, ultrasound, and magnetic resonance imaging present opportunities to improve the diagnosis and preoperative assessment of ILC. The evidence supporting the performance of each imaging modality will be reviewed, specifically as it relates to the pathology of ILC and its subtypes. Further, we will discuss emerging technologies that may be employed to enhance the detection rate and ultimately result in more effective screening and staging of ILC.

Authors
Johnson, K; Sarma, D; Hwang, ES
MLA Citation
Johnson, K, Sarma, D, and Hwang, ES. "Lobular breast cancer series: imaging." Breast cancer research : BCR 17 (January 2015): 94-. (Review)
PMID
26163296
Source
epmc
Published In
Breast Cancer Research
Volume
17
Publish Date
2015
Start Page
94
DOI
10.1186/s13058-015-0605-0

Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells.

Blockade of colony-stimulating factor-1 (CSF-1) limits macrophage infiltration and improves response of mammary carcinomas to chemotherapy. Herein we identify interleukin (IL)-10 expression by macrophages as the critical mediator of this phenotype. Infiltrating macrophages were the primary source of IL-10 within tumors, and therapeutic blockade of IL-10 receptor (IL-10R) was equivalent to CSF-1 neutralization in enhancing primary tumor response to paclitaxel and carboplatin. Improved response to chemotherapy was CD8(+) T cell-dependent, but IL-10 did not directly suppress CD8(+) T cells or alter macrophage polarization. Instead, IL-10R blockade increased intratumoral dendritic cell expression of IL-12, which was necessary for improved outcomes. In human breast cancer, expression of IL12A and cytotoxic effector molecules were predictive of pathological complete response rates to paclitaxel.

Authors
Ruffell, B; Chang-Strachan, D; Chan, V; Rosenbusch, A; Ho, CMT; Pryer, N; Daniel, D; Hwang, ES; Rugo, HS; Coussens, LM
MLA Citation
Ruffell, B, Chang-Strachan, D, Chan, V, Rosenbusch, A, Ho, CMT, Pryer, N, Daniel, D, Hwang, ES, Rugo, HS, and Coussens, LM. "Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells." Cancer cell 26.5 (November 2014): 623-637.
PMID
25446896
Source
epmc
Published In
Cancer Cell
Volume
26
Issue
5
Publish Date
2014
Start Page
623
End Page
637
DOI
10.1016/j.ccell.2014.09.006

Total skin-sparing mastectomy and immediate breast reconstruction: an evolution of technique and assessment of outcomes.

BACKGROUND: Total skin-sparing mastectomy (TSSM) with preservation of the breast and nipple-areolar complex (NAC) skin was developed to improve aesthetic outcomes for mastectomy. Over time, indications for TSSM broadened and our technique has evolved with a series of systematic improvements. METHODS: We reviewed all cases of TSSM with immediate breast reconstruction performed from 2005 to 2012. Patient comorbidities, treatment characteristics, postoperative complications, and outcomes were obtained prospectively and through medical chart review. Locoregional recurrences, distant recurrences, and patient survival were analyzed with Kaplan-Meier methods. RESULTS: During this 8-year period, 633 patients (981 cases) underwent TSSM with median follow-up time of 29 (interquartile range 14-54) months. Immediate breast reconstruction was performed with tissue expander placement (89 %), pedicle TRAM (5 %), free flap (5 %), permanent implant (0.3 %), or latissimus flap (0.2 %). The incidences of postoperative complications decreased significantly over time. In 2012, these were down to 3.5 % for superficial nipple necrosis, 1.0 % for complete nipple necrosis, 3.0 % for minor skin flap necrosis, 4.4 % for major skin flap necrosis, 13.3 % for infections requiring oral antibiotics, 9.9 % for infections requiring intravenous antibiotics, 3.4 % for infections requiring operative intervention, and 8.5 % for expander/implant. Overall 5-year cumulative incidences of recurrence were 3.0 % (locoregional) and 4.2 % (distant), and there were no recurrences in the NAC skin. CONCLUSIONS: Systematic changes in our technique of TSSM and immediate breast reconstruction have decreased postoperative complications over time. Oncologic outcomes of locoregional and distal recurrences remain similar to skin-sparing mastectomy techniques.

Authors
Wang, F; Peled, AW; Garwood, E; Fiscalini, AS; Sbitany, H; Foster, RD; Alvarado, M; Ewing, C; Hwang, ES; Esserman, LJ
MLA Citation
Wang, F, Peled, AW, Garwood, E, Fiscalini, AS, Sbitany, H, Foster, RD, Alvarado, M, Ewing, C, Hwang, ES, and Esserman, LJ. "Total skin-sparing mastectomy and immediate breast reconstruction: an evolution of technique and assessment of outcomes." Annals of surgical oncology 21.10 (October 2014): 3223-3230.
PMID
25052246
Source
epmc
Published In
Annals of Surgical Oncology
Volume
21
Issue
10
Publish Date
2014
Start Page
3223
End Page
3230
DOI
10.1245/s10434-014-3915-z

New Therapeutic Approaches for Invasive Lobular Carcinoma

Authors
Hwang, ES
MLA Citation
Hwang, ES. "New Therapeutic Approaches for Invasive Lobular Carcinoma." Current Breast Cancer Reports 6.3 (September 2014): 159-168.
Source
crossref
Published In
Current Breast Cancer Reports
Volume
6
Issue
3
Publish Date
2014
Start Page
159
End Page
168
DOI
10.1007/s12609-014-0158-8

In defense of screening for breast cancer with magnetic resonance imaging--reply.

Authors
Hwang, ES
MLA Citation
Hwang, ES. "In defense of screening for breast cancer with magnetic resonance imaging--reply." JAMA internal medicine 174.8 (August 2014): 1417-1418. (Letter)
PMID
25090184
Source
epmc
Published In
JAMA Internal Medicine
Volume
174
Issue
8
Publish Date
2014
Start Page
1417
End Page
1418
DOI
10.1001/jamainternmed.2014.803

Breast conservation: is the survival better for mastectomy?

Breast conserving therapy with radiation is now firmly established as an effective treatment option for early stage disease, and has been thought for decades to yield equivalent survival outcomes to mastectomy. However, recently published observational studies as well as meta-analyses suggest not only a locoregional, but possibly a systemic benefit to BCT. Choice of surgery and radiation is only one of numerous factors impacting survival following surgery for early stage breast cancer; competing comorbidities and risk of treatment related side effects from radiotherapy must also be considered in order to make optimal treatment recommendations.

Authors
Hwang, ES
MLA Citation
Hwang, ES. "Breast conservation: is the survival better for mastectomy?." Journal of surgical oncology 110.1 (July 2014): 58-61. (Review)
PMID
24846595
Source
epmc
Published In
Journal of Surgical Oncology
Volume
110
Issue
1
Publish Date
2014
Start Page
58
End Page
61
DOI
10.1002/jso.23622

Risk of positive nonsentinel nodes in women with 1-2 positive sentinel nodes related to age and molecular subtype approximated by receptor status.

We examine risk of positive nonsentinel axillary nodes (NSN) and ≥4 positive nodes in patients with 1-2 positive sentinel nodes (SN) by age and tumor subtype approximated by ER, PR, and Her2 receptor status. Review of two institutional databases demonstrated 284 women undergoing breast conservation between 1997 and 2008 for T1-2 tumors and 1 (229) or 2 (55) positive SN followed by completion dissection. The median number of SN and total axillary nodes removed were 2 (range 1-10) and 14 (range 6-37), respectively. The rate of positive NSNs (p = 0.5) or ≥4 positive nodes (p = 0.6) was not associated with age. NSN were positive in 36% of luminal A, 26% of luminal B, 21% of TN and 38% of Her2+ (p = 0.4). Four or more nodes were present in 17% of luminal A, 13% luminal of B, 0% of TN and 29% of Her2+ (p = 0.1). Microscopic extracapsular extension was significantly associated with having NSNs positive (55% versus 24%, p < 0.0001) and with having total ≥4 nodes positive (33% versus 7%, p < 0.0001). In a population that was largely eligible for ACOSOG Z0011, the risk of positive NSN or ≥4 positive nodes did not vary significantly by age. The TN subgroup had the lowest risk of both positive NSN or ≥4 positive nodes. Several high risk groups with >15% risk for having ≥4 positive nodes were identified. Further data is needed to confirm that ACOSOG Z0011 results are equally applicable to all molecular phenotypes.

Authors
Freedman, GM; Fowble, BL; Li, T; Hwang, ES; Schechter, N; Devarajan, K; Anderson, PR; Sigurdson, ER; Goldstein, LJ; Bleicher, RJ
MLA Citation
Freedman, GM, Fowble, BL, Li, T, Hwang, ES, Schechter, N, Devarajan, K, Anderson, PR, Sigurdson, ER, Goldstein, LJ, and Bleicher, RJ. "Risk of positive nonsentinel nodes in women with 1-2 positive sentinel nodes related to age and molecular subtype approximated by receptor status." The breast journal 20.4 (July 2014): 358-363.
PMID
24861613
Source
epmc
Published In
The Breast Journal
Volume
20
Issue
4
Publish Date
2014
Start Page
358
End Page
363
DOI
10.1111/tbj.12276

Patient-reported outcomes and satisfaction after total skin-sparing mastectomy and immediate expander-implant reconstruction.

BACKGROUND: Total skin-sparing mastectomy (TSSM) with preservation of the nipple-areolar complex skin has become more widely accepted. Few studies looking at outcomes after TSSM and immediate reconstruction have focused on patient-reported outcomes and trends in satisfaction over time. METHODS: Prospective evaluation of patients undergoing TSSM and immediate expander-implant reconstruction was performed. Patients completed the BREAST-Q questionnaire preoperatively and again at 1 month, 6 months, and 1 year postoperatively. Mean scores in each BREAST-Q domain were assessed at each time point. Domains were scored on a 0- to 100-point scale. RESULTS: Survey completion rate was 55%; BREAST-Q scores were calculated from responses from 28 patients. Mean overall satisfaction with breasts declined at 1 month (69.8 to 46.1, P<0.001), but then returned to baseline by 1 year. Mean scores also declined at 1 month in the psychosocial (75.7-67.4, P=0.2) and sexual (58.3-46.7, P=0.06) domains, but returned to baseline by 1 year. Mean nipple satisfaction score was 76.4 at 1 year, with 89% of patients reporting satisfaction with nipple appearance. Satisfaction with nipple position and sensation was lower, with only 56% of patients reporting satisfaction with nipple position and 40% with nipple sensation. CONCLUSIONS: After TSSM and immediate reconstruction, patient satisfaction with their breasts, as well as psychosocial and sexual well-being, returns to baseline by 1 year. Although overall nipple satisfaction is high, patients often report dissatisfaction with nipple position and sensation; appropriate preoperative counseling is important to set realistic expectations.

Authors
Peled, AW; Duralde, E; Foster, RD; Fiscalini, AS; Esserman, LJ; Hwang, ES; Sbitany, H
MLA Citation
Peled, AW, Duralde, E, Foster, RD, Fiscalini, AS, Esserman, LJ, Hwang, ES, and Sbitany, H. "Patient-reported outcomes and satisfaction after total skin-sparing mastectomy and immediate expander-implant reconstruction." Ann Plast Surg 72 Suppl 1 (May 2014): S48-S52.
PMID
24317238
Source
pubmed
Published In
Annals of Plastic Surgery
Volume
72 Suppl 1
Publish Date
2014
Start Page
S48
End Page
S52
DOI
10.1097/SAP.0000000000000020

Cost implications of the SSO-ASTRO consensus guideline on margins for breast-conserving surgery with whole breast irradiation in stage I and II invasive breast cancer.

Authors
Greenup, RA; Peppercorn, J; Worni, M; Hwang, ES
MLA Citation
Greenup, RA, Peppercorn, J, Worni, M, and Hwang, ES. "Cost implications of the SSO-ASTRO consensus guideline on margins for breast-conserving surgery with whole breast irradiation in stage I and II invasive breast cancer." Annals of surgical oncology 21.5 (May 2014): 1512-1514.
PMID
24577813
Source
epmc
Published In
Annals of Surgical Oncology
Volume
21
Issue
5
Publish Date
2014
Start Page
1512
End Page
1514
DOI
10.1245/s10434-014-3605-x

Cost Implications of the SSO-ASTRO Consensus Guideline on Margins for Breast-Conserving Surgery with Whole Breast Irradiation in Stage I and II Invasive Breast Cancer

Authors
Greenup, RA; Peppercorn, J; Worni, M; Hwang, ES
MLA Citation
Greenup, RA, Peppercorn, J, Worni, M, and Hwang, ES. "Cost Implications of the SSO-ASTRO Consensus Guideline on Margins for Breast-Conserving Surgery with Whole Breast Irradiation in Stage I and II Invasive Breast Cancer." Annals of Surgical Oncology 21.5 (May 2014): 1512-1514.
Source
crossref
Published In
Annals of Surgical Oncology
Volume
21
Issue
5
Publish Date
2014
Start Page
1512
End Page
1514
DOI
10.1245/s10434-014-3605-x

Addressing overdiagnosis and overtreatment in cancer: a prescription for change.

A vast range of disorders--from indolent to fast-growing lesions--are labelled as cancer. Therefore, we believe that several changes should be made to the approach to cancer screening and care, such as use of new terminology for indolent and precancerous disorders. We propose the term indolent lesion of epithelial origin, or IDLE, for those lesions (currently labelled as cancers) and their precursors that are unlikely to cause harm if they are left untreated. Furthermore, precursors of cancer or high-risk disorders should not have the term cancer in them. The rationale for this change in approach is that indolent lesions with low malignant potential are common, and screening brings indolent lesions and their precursors to clinical attention, which leads to overdiagnosis and, if unrecognised, possible overtreatment. To minimise that potential, new strategies should be adopted to better define and manage IDLEs. Screening guidelines should be revised to lower the chance of detection of minimal-risk IDLEs and inconsequential cancers with the same energy traditionally used to increase the sensitivity of screening tests. Changing the terminology for some of the lesions currently referred to as cancer will allow physicians to shift medicolegal notions and perceived risk to reflect the evolving understanding of biology, be more judicious about when a biopsy should be done, and organise studies and registries that offer observation or less invasive approaches for indolent disease. Emphasis on avoidance of harm while assuring benefit will improve screening and treatment of patients and will be equally effective in the prevention of death from cancer.

Authors
Esserman, LJ; Thompson, IM; Reid, B; Nelson, P; Ransohoff, DF; Welch, HG; Hwang, S; Berry, DA; Kinzler, KW; Black, WC; Bissell, M; Parnes, H; Srivastava, S
MLA Citation
Esserman, LJ, Thompson, IM, Reid, B, Nelson, P, Ransohoff, DF, Welch, HG, Hwang, S, Berry, DA, Kinzler, KW, Black, WC, Bissell, M, Parnes, H, and Srivastava, S. "Addressing overdiagnosis and overtreatment in cancer: a prescription for change." The Lancet. Oncology 15.6 (May 2014): e234-e242.
PMID
24807866
Source
epmc
Published In
The Lancet Oncology
Volume
15
Issue
6
Publish Date
2014
Start Page
e234
End Page
e242
DOI
10.1016/s1470-2045(13)70598-9

The current clinical value of the DCIS Score.

The management of ductal carcinoma in situ (DCIS) can be controversial. Widespread adoption of mammographic screening has made DCIS a more frequent diagnosis, and increasingly smaller, lower-grade lesions are being detected. DCIS is commonly treated with breast-conserving surgery and radiation. However, there is greater recognition that acceptable cancer control outcomes can be achieved for some patients with breast-conserving surgery alone, with radiotherapy reserved for those at higher risk of in-breast recurrence. The primary clinical dilemma is that there are currently no reliable clinicopathologic features that accurately predict which patients will have a recurrence, but risk stratification is an area of active research. Molecular profiling has the potential to assess recurrence risk based on the individual patient's tumor biology and guide treatment decisions. The DCIS Score is a 12-gene assay intended to support personalized treatment planning for patients with DCIS following local excision. It provides information on local failure risk independent of traditional clinicopathologic features. Our group of expert breast surgeons and radiation oncologists met in December 2013 at the San Antonio Breast Cancer Symposium to discuss current controversies in DCIS management and determine the potential value of the DCIS Score in managing these situations. We concluded that the DCIS Score provides clinically relevant information about personal risk that can guide patient discussions and facilitate shared decision making.

Authors
Wood, WC; Alvarado, M; Buchholz, DJ; Hyams, D; Hwang, S; Manders, J; Park, C; Solin, LJ; White, J; Willey, S
MLA Citation
Wood, WC, Alvarado, M, Buchholz, DJ, Hyams, D, Hwang, S, Manders, J, Park, C, Solin, LJ, White, J, and Willey, S. "The current clinical value of the DCIS Score." May 2014.
PMID
25375000
Source
epmc
Published In
Oncology
Volume
28 Suppl 2
Publish Date
2014
Start Page
C2
End Page
C3

Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression.

Tissue mechanics regulate development and homeostasis and are consistently modified in tumor progression. Nevertheless, the fundamental molecular mechanisms through which altered mechanics regulate tissue behavior and the clinical relevance of these changes remain unclear. We demonstrate that increased matrix stiffness modulates microRNA expression to drive tumor progression through integrin activation of β-catenin and MYC. Specifically, in human and mouse tissue, increased matrix stiffness induced miR-18a to reduce levels of the tumor suppressor phosphatase and tensin homolog (PTEN), both directly and indirectly by decreasing levels of homeobox A9 (HOXA9). Clinically, extracellular matrix stiffness correlated directly and significantly with miR-18a expression in human breast tumor biopsies. miR-18a expression was highest in basal-like breast cancers in which PTEN and HOXA9 levels were lowest, and high miR-18a expression predicted poor prognosis in patients with luminal breast cancers. Our findings identify a mechanically regulated microRNA circuit that can promote malignancy and suggest potential prognostic roles for HOXA9 and miR-18a levels in stratifying patients with luminal breast cancers.

Authors
Mouw, JK; Yui, Y; Damiano, L; Bainer, RO; Lakins, JN; Acerbi, I; Ou, G; Wijekoon, AC; Levental, KR; Gilbert, PM; Hwang, ES; Chen, Y-Y; Weaver, VM
MLA Citation
Mouw, JK, Yui, Y, Damiano, L, Bainer, RO, Lakins, JN, Acerbi, I, Ou, G, Wijekoon, AC, Levental, KR, Gilbert, PM, Hwang, ES, Chen, Y-Y, and Weaver, VM. "Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression." Nature medicine 20.4 (April 2014): 360-367.
PMID
24633304
Source
epmc
Published In
Nature Medicine
Volume
20
Issue
4
Publish Date
2014
Start Page
360
End Page
367
DOI
10.1038/nm.3497

Incidence Patterns of Breast Cancer among Women 35 and Younger at Diagnosis

Authors
Greenup, RA; Arbeev, K; Akushevich, I; Mackey, A; Tolnitch, L; Hwang, ES
MLA Citation
Greenup, RA, Arbeev, K, Akushevich, I, Mackey, A, Tolnitch, L, and Hwang, ES. "Incidence Patterns of Breast Cancer among Women 35 and Younger at Diagnosis." February 2014.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
21
Publish Date
2014
Start Page
S56
End Page
S57

The Cumulative Impact of Breast Irradiation on Chest Wall Angiosarcoma: A 40-year Outcome Study

Authors
Mackey, A; Arbeev, K; Akushevich, I; Greenup, R; Georgiade, G; Horton, J; Brennan, MF; Hwang, ES
MLA Citation
Mackey, A, Arbeev, K, Akushevich, I, Greenup, R, Georgiade, G, Horton, J, Brennan, MF, and Hwang, ES. "The Cumulative Impact of Breast Irradiation on Chest Wall Angiosarcoma: A 40-year Outcome Study." February 2014.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
21
Publish Date
2014
Start Page
S10
End Page
S10

Satisfaction with treatment decision-making and treatment regret among Latinas and non-Latina whites with DCIS

Objective: To examine differences in treatment decision-making participation, satisfaction, and regret among Latinas and non-Latina whites with DCIS. Methods: Survey of Latina and non-Latina white women diagnosed with DCIS. We assessed women's preferences for involvement in decision-making, primary treatment decision maker, and participatory decision-making. We examined primary outcomes of satisfaction with treatment decision-making and treatment regret by ethnic-language group. Results: Among 745 participants (349 Latinas, 396 white) Spanish-speaking Latinas (SSL) had the highest mean preference for involvement in decision-making score and the lowest mean participatory decision-making score and were more likely to defer their final treatment decision to their physicians than English-speaking Latinas or whites (26%, 13%, 18%, p < 0.05). SSLs reported lower satisfaction with treatment decision-making (OR 0.4; CI 95%, 0.2-0.8) and expressed more regret than whites (OR 6.2; CI 95%, 3.0-12.4). More participatory decision-making increased the odds of satisfaction (OR 1.5; CI 95%, 1.3-1.8) and decreased the odds of treatment regret (OR 0.8; CI 95%, 0.7-1.0), independent of ethnicity-language. Conclusion: Language barriers impede the establishment of decision-making partnerships between Latinas and their physicians, and result in less satisfaction with the decision-making process and more treatment regret. Practice implications: Use of professional interpreters may address communication-related disparities for these women. © 2013 Elsevier Ireland Ltd.

Authors
López, ME; Kaplan, CP; Nápoles, AM; Hwang, ES; Livaudais, JC; Karliner, LS
MLA Citation
López, ME, Kaplan, CP, Nápoles, AM, Hwang, ES, Livaudais, JC, and Karliner, LS. "Satisfaction with treatment decision-making and treatment regret among Latinas and non-Latina whites with DCIS." Patient Education and Counseling 94.1 (January 1, 2014): 83-89.
Source
scopus
Published In
Patient Education and Counseling
Volume
94
Issue
1
Publish Date
2014
Start Page
83
End Page
89
DOI
10.1016/j.pec.2013.09.005

Total skin-sparing mastectomy in BRCA mutation carriers

Background: Total skin-sparing mastectomy (TSSM) with preservation of the nipple-areolar complex skin has become increasingly accepted as an oncologically safe procedure. Oncologic outcomes after TSSM in BRCA mutation carriers have not been well-studied. Methods: We identified 53 BRCA-positive patients who underwent bilateral TSSM for prophylactic (26 patients) or therapeutic indications (27 patients) from 2001 to 2011. Cases were age-matched (for prophylactic cases) or age- and stage-matched (for therapeutic cases) with non-BRCA-positive patients. Outcomes included tumor involvement of resected nipple tissue, the development of new breast cancers in patients who underwent risk-reducing TSSM, and local-regional recurrence in patients who underwent therapeutic TSSM. Results: Outcomes from 212 TSSM procedures in 53 cases and 53 controls were analyzed. In patients undergoing TSSM for prophylactic indications, in situ cancer was found in one (1.9 %) nipple specimen in BRCA-positive patients versus two specimens (3.8 %) in the non-BRCA-positive cohort (p = 1). At a mean follow-up of 51 months, no new cancers developed in either cohort. In patients undergoing TSSM for therapeutic indications, in situ or invasive cancer was found in zero of the nipple specimens in BRCA-positive patients versus two specimens (3.7 %) in the non-BRCA-positive cohort (p = 0.49). At a mean follow-up of 37 months, there were no local-regional recurrences in the BRCA-positive cohort and 1 (3.7 %) in the non-BRCA-positive cohort. Conclusions: TSSM is an oncologically safe procedure in BRCA-positive patients. In patients undergoing TSSM as a risk-reducing strategy, 4-year follow-up demonstrates no increased risk of developing new breast cancers; longer-term follow-up is ongoing. © 2013 Society of Surgical Oncology.

Authors
Peled, AW; Irwin, CS; Hwang, ES; Ewing, CA; Alvarado, M; Esserman, LJ
MLA Citation
Peled, AW, Irwin, CS, Hwang, ES, Ewing, CA, Alvarado, M, and Esserman, LJ. "Total skin-sparing mastectomy in BRCA mutation carriers." Annals of Surgical Oncology 21.1 (January 1, 2014): 37-41.
Source
scopus
Published In
Annals of Surgical Oncology
Volume
21
Issue
1
Publish Date
2014
Start Page
37
End Page
41
DOI
10.1245/s10434-013-3230-0

Should ductal carcinoma in situ be treated?

Authors
Kuerer, HM; Hwang, ES
MLA Citation
Kuerer, HM, and Hwang, ES. "Should ductal carcinoma in situ be treated?." Oncology Report 10.11 (January 1, 2014): 8-10.
Source
scopus
Published In
Oncology Report
Volume
10
Issue
11
Publish Date
2014
Start Page
8
End Page
10

Patterns of breast magnetic resonance imaging use: an opportunity for data-driven resource allocation.

Authors
Hwang, ES; Bedrosian, I
MLA Citation
Hwang, ES, and Bedrosian, I. "Patterns of breast magnetic resonance imaging use: an opportunity for data-driven resource allocation." JAMA Intern Med 174.1 (January 2014): 122-124.
PMID
24247170
Source
pubmed
Published In
JAMA Internal Medicine
Volume
174
Issue
1
Publish Date
2014
Start Page
122
End Page
124
DOI
10.1001/jamainternmed.2013.10502

Abstract P5-14-04: Preoperative single-fraction partial breast radiotherapy – Initial results from a novel phase I dose-escalation protocol with exploration of radiation response biomarkers

Authors
Horton, JK; Blitzblau, RC; Yoo, S; Georgiade, GS; Geradts, J; Baker, JA; Chang, Z; Broadwater, G; Barry, W; Duffy, EA; Hwang, ES
MLA Citation
Horton, JK, Blitzblau, RC, Yoo, S, Georgiade, GS, Geradts, J, Baker, JA, Chang, Z, Broadwater, G, Barry, W, Duffy, EA, and Hwang, ES. "Abstract P5-14-04: Preoperative single-fraction partial breast radiotherapy – Initial results from a novel phase I dose-escalation protocol with exploration of radiation response biomarkers." December 15, 2013.
Source
crossref
Published In
Cancer Research
Volume
73
Issue
24 Supplement
Publish Date
2013
Start Page
P5-14-04
End Page
P5-14-04
DOI
10.1158/0008-5472.SABCS13-P5-14-04

Features of occult invasion in biopsy-proven DCIS at breast MRI

The purpose of this study is to determine if MRI BI-RADS criteria or radiologist perception correlate with presence of invasive cancer after initial core biopsy of ductal carcinoma in situ (DCIS). Retrospective search spanning 2000-2007 identified all core-biopsy diagnoses of pure DCIS that coincided with preoperative MRI. Two radiologists fellowship-trained in breast imaging categorized lesions according to ACR MRI BI-RADS lexicon and estimated likelihood of occult invasion. Semiquantitative signal enhancement ratio (SER) kinetic analysis was also performed. Results were compared with histopathology. 51 consecutive patients with primary core biopsy-proven DCIS and concurrent MRI were identified. Of these, 13 patients (25%) had invasion at excision. Invasion correlated significantly with presence of a mass for both readers (p = 0.012 and 0.001), rapid initial enhancement for Reader 1 (p = 0.001), and washout kinetics for Reader 2 (p = 0.012). Significant correlation between washout and invasion was confirmed by SER (p = 0.006) when threshold percent enhancement was sufficiently high (130%), corresponding to rapidly enhancing portions of the lesion. Radiologist perception of occult invasion was strongly correlated with true presence of invasion. These results provide evidence that certain BI-RADS MRI criteria, as well as radiologist perception, correlate with occult invasion after an initial core biopsy of DCIS. © 2013 Wiley Periodicals, Inc.

Authors
Wisner, DJ; Hwang, ES; Chang, CB; Tso, HH; Joe, BN; Lessing, JN; Lu, Y; Hylton, NM
MLA Citation
Wisner, DJ, Hwang, ES, Chang, CB, Tso, HH, Joe, BN, Lessing, JN, Lu, Y, and Hylton, NM. "Features of occult invasion in biopsy-proven DCIS at breast MRI." Breast Journal 19.6 (November 1, 2013): 650-658.
PMID
24165314
Source
scopus
Published In
The Breast Journal
Volume
19
Issue
6
Publish Date
2013
Start Page
650
End Page
658
DOI
10.1111/tbj.12201

Impact of ductal carcinoma in situ terminology on patient treatment preferences

Authors
Omer, ZB; Hwang, ES; Esserman, LJ; Howe, R; Ozanne, EM
MLA Citation
Omer, ZB, Hwang, ES, Esserman, LJ, Howe, R, and Ozanne, EM. "Impact of ductal carcinoma in situ terminology on patient treatment preferences." JAMA Internal Medicine 173.19 (October 28, 2013): 1830-1831. (Letter)
PMID
23978843
Source
scopus
Published In
JAMA Internal Medicine
Volume
173
Issue
19
Publish Date
2013
Start Page
1830
End Page
1831
DOI
10.1001/jamainternmed.2013.8405

Preoperative Single:Fraction Partial Breast Radiation Therapy: A Novel Phase 1 Dose-Escalation Protocol and Exploration of Breast Cancer Radiation Response

Authors
Horton, JK; Blitzblau, RC; Yoo, S; Georgiade, GS; Geradts, J; Baker, JA; Chang, Z; Duffy, E; Hwang, ES
MLA Citation
Horton, JK, Blitzblau, RC, Yoo, S, Georgiade, GS, Geradts, J, Baker, JA, Chang, Z, Duffy, E, and Hwang, ES. "Preoperative Single:Fraction Partial Breast Radiation Therapy: A Novel Phase 1 Dose-Escalation Protocol and Exploration of Breast Cancer Radiation Response." October 1, 2013.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
87
Issue
2
Publish Date
2013
Start Page
S229
End Page
S229

Reply to survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status.

Authors
Hwang, ES; Clarke, CA; Gomez, SL
MLA Citation
Hwang, ES, Clarke, CA, and Gomez, SL. "Reply to survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status." Cancer 119.17 (September 1, 2013): 3254-3255. (Letter)
PMID
23824869
Source
pubmed
Published In
Cancer
Volume
119
Issue
17
Publish Date
2013
Start Page
3254
End Page
3255
DOI
10.1002/cncr.28181

Ductal carcinoma in situ: knowledge of associated risks and prognosis among Latina and non-Latina white women

Authors
Parikh, AR; Kaplan, CP; Burke, NJ; Livaudais-Toman, J; Hwang, ES; Karliner, LS
MLA Citation
Parikh, AR, Kaplan, CP, Burke, NJ, Livaudais-Toman, J, Hwang, ES, and Karliner, LS. "Ductal carcinoma in situ: knowledge of associated risks and prognosis among Latina and non-Latina white women." BREAST CANCER RESEARCH AND TREATMENT 141.2 (September 2013): 261-268.
PMID
23996141
Source
wos-lite
Published In
Breast Cancer Research and Treatment
Volume
141
Issue
2
Publish Date
2013
Start Page
261
End Page
268
DOI
10.1007/s10549-013-2676-x

Change in mammographic density with metformin use: A companion study to NCIC study MA.32.

Authors
Wood, ME; Qin, R; Le-Petross, HT; Hwang, ES; Ligibel, JA; Mayer, IA; Marshall, JR; Goodwin, PJ
MLA Citation
Wood, ME, Qin, R, Le-Petross, HT, Hwang, ES, Ligibel, JA, Mayer, IA, Marshall, JR, and Goodwin, PJ. "Change in mammographic density with metformin use: A companion study to NCIC study MA.32." May 20, 2013.
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
31
Issue
15
Publish Date
2013

Survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status.

BACKGROUND: Randomized clinical trials (RCT) have demonstrated equivalent survival for breast-conserving therapy with radiation (BCT) and mastectomy for early-stage breast cancer. A large, population-based series of women who underwent BCT or mastectomy was studied to observe whether outcomes of RCT were achieved in the general population, and whether survival differed by surgery type when stratified by age and hormone receptor (HR) status. METHODS: Information was obtained regarding all women diagnosed in the state of California with stage I or II breast cancer between 1990 and 2004, who were treated with either BCT or mastectomy and followed for vital status through December 2009. Cox proportional hazards modeling was used to compare overall survival (OS) and disease-specific survival (DSS) between BCT and mastectomy groups. Analyses were stratified by age group (< 50 years and ≥ 50 years) and tumor HR status. RESULTS: A total of 112,154 women fulfilled eligibility criteria. Women undergoing BCT had improved OS and DSS compared with women with mastectomy (adjusted hazard ratio for OS entire cohort = 0.81, 95% confidence interval [CI] = 0.80-0.83). The DSS benefit with BCT compared with mastectomy was greater among women age ≥ 50 with HR-positive disease (hazard ratio = 0.86, 95% CI = 0.82-0.91) than among women age < 50 with HR-negative disease (hazard ratio = 0.88, 95% CI = 0.79-0.98); however, this trend was seen among all subgroups analyzed. CONCLUSIONS: Among patients with early stage breast cancer, BCT was associated with improved DSS. These data provide confidence that BCT remains an effective alternative to mastectomy for early stage disease regardless of age or HR status.

Authors
Hwang, ES; Lichtensztajn, DY; Gomez, SL; Fowble, B; Clarke, CA
MLA Citation
Hwang, ES, Lichtensztajn, DY, Gomez, SL, Fowble, B, and Clarke, CA. "Survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status." Cancer 119.7 (April 1, 2013): 1402-1411.
PMID
23359049
Source
pubmed
Published In
Cancer
Volume
119
Issue
7
Publish Date
2013
Start Page
1402
End Page
1411
DOI
10.1002/cncr.27795

Multidisciplinary care of patients with early-stage breast cancer.

There is a compelling need for close coordination and integration of multiple specialties in the management of patients with early-stage breast cancer. Optimal patient care and outcomes depend on the sequential and often simultaneous participation and dialogue between specialists in imaging, pathologic and molecular diagnostic and prognostic stratification, and the therapeutic specialties of surgery, radiation oncology, and medical oncology. These are but a few of the various disciplines needed to provide modern, sophisticated management. The essential role for coordinated involvement of the entire health care team in optimal management of patients with early-stage breast cancer is likely to increase further.

Authors
Lyman, GH; Baker, J; Geradts, J; Horton, J; Kimmick, G; Peppercorn, J; Pruitt, S; Scheri, RP; Hwang, ES
MLA Citation
Lyman, GH, Baker, J, Geradts, J, Horton, J, Kimmick, G, Peppercorn, J, Pruitt, S, Scheri, RP, and Hwang, ES. "Multidisciplinary care of patients with early-stage breast cancer." Surg Oncol Clin N Am 22.2 (April 2013): 299-317. (Review)
PMID
23453336
Source
pubmed
Published In
Surgical Oncology Clinics of North America
Volume
22
Issue
2
Publish Date
2013
Start Page
299
End Page
317
DOI
10.1016/j.soc.2012.12.005

Impact of Race in Prevalence of BRCA Mutations Among Women With Triple-Negative Breast Cancer (TNBC) in a Genetic Counseling Cohort

Authors
Greenup, R; Marcom, PK; McLennan, J; Buchanan, A; King, R; Crawford, B; Chen, Y-Y; Mackey, A; Hwang, ES
MLA Citation
Greenup, R, Marcom, PK, McLennan, J, Buchanan, A, King, R, Crawford, B, Chen, Y-Y, Mackey, A, and Hwang, ES. "Impact of Race in Prevalence of BRCA Mutations Among Women With Triple-Negative Breast Cancer (TNBC) in a Genetic Counseling Cohort." April 2013.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
20
Publish Date
2013
Start Page
17
End Page
17

Contralateral Prophylactic Mastectomy for Unilateral Breast Cancer: A Review of the National Comprehensive Cancer Network (NCCN) Database

Authors
Carson, WE; Otteson, RA; Hughes, ME; Neumayer, L; Hwang, ES; Laronga, C; Breslin, T; Chen, SL; Khan, S; Edge, SB; Farrar, WB; Weeks, JC
MLA Citation
Carson, WE, Otteson, RA, Hughes, ME, Neumayer, L, Hwang, ES, Laronga, C, Breslin, T, Chen, SL, Khan, S, Edge, SB, Farrar, WB, and Weeks, JC. "Contralateral Prophylactic Mastectomy for Unilateral Breast Cancer: A Review of the National Comprehensive Cancer Network (NCCN) Database." February 2013.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
20
Publish Date
2013
Start Page
S10
End Page
S10

Outcomes after Mastectomy for Node-positive Breast Cancer: Comparison of Women Treated With and Without Completion Axillary Dissection at NCCN Cancer Centers

Authors
Greenup, RA; Breslin, T; Edge, SB; Hughes, ME; Hwang, ES; Laronga, C; Marcom, P; Moy, B; Otteson, RA; Rugo, H; Wilson, JL; Wong, Y; Weeks, JC
MLA Citation
Greenup, RA, Breslin, T, Edge, SB, Hughes, ME, Hwang, ES, Laronga, C, Marcom, P, Moy, B, Otteson, RA, Rugo, H, Wilson, JL, Wong, Y, and Weeks, JC. "Outcomes after Mastectomy for Node-positive Breast Cancer: Comparison of Women Treated With and Without Completion Axillary Dissection at NCCN Cancer Centers." February 2013.
Source
wos-lite
Published In
Annals of Surgical Oncology
Volume
20
Publish Date
2013
Start Page
S9
End Page
S9

Prevalence of BRCA mutations among women with triple-negative breast cancer (TNBC) in a genetic counseling cohort

Background: Revised NCCN guidelines recommend that women ≤60 years with triple-negative breast cancer (TNBC) be referred for consideration of genetic counseling. Small, homogeneous samples have limited evaluation of BRCA mutation prevalence among different ethnicities affected by TNBC subtype. We sought to determine whether the prevalence of BRCA mutations within a TNBC cohort differs by demographic factors. Methods: We performed a retrospective review of patients with TNBC referred for genetic counseling at two academic Hereditary Cancer Clinics between 2000 and 2012. Demographic data were collected, including age at diagnosis and race/ethnicity. Race was categorized as African American (AA), Ashkenazi Jewish (AJ), Asian, Caucasian, Hispanic, or other. Primary outcome was BRCA mutation status, analyzed by race/ethnicity and age at diagnosis. Results: A total of 469 patients with TNBC who underwent testing for BRCA genetic mutations were identified, of which 450 patients had evaluable BRCA testing results; 139 (30.8 %) had confirmed BRCA1 (n = 106) or BRCA2 (n = 32) mutations. BRCA mutation prevalence differed by ethnicity and race: AA (20.4 %), AJ (50 %), Asian (28.5 %), Caucasian (33.3 %), and Hispanic (20 %). The prevalence of genetic mutations also differed by age at diagnosis: <40 years (43.8 %), 40-49 years (27.4 %), 50-59 years (25.3 %), 60-69 years (12.5 %), and >70 years (16.6 %). Conclusions: The prevalence of genetic mutations among women with TNBC referred for genetic counseling is high and differs significantly by ethnicity/race and age. This data helps to refine mutation risk estimates among women with TNBC, allowing for more personalized genetic counseling potentially aiding in improved patient decision-making. © 2013 Society of Surgical Oncology.

Authors
Greenup, R; Buchanan, A; Lorizio, W; Rhoads, K; Chan, S; Leedom, T; King, R; McLennan, J; Crawford, B; Marcom, PK; al, E
MLA Citation
Greenup, R, Buchanan, A, Lorizio, W, Rhoads, K, Chan, S, Leedom, T, King, R, McLennan, J, Crawford, B, Marcom, PK, and al, E. "Prevalence of BRCA mutations among women with triple-negative breast cancer (TNBC) in a genetic counseling cohort." Annals of Surgical Oncology 20.10 (2013): 3254-3258.
Source
scival
Published In
Annals of Surgical Oncology
Volume
20
Issue
10
Publish Date
2013
Start Page
3254
End Page
3258
DOI
10.1245/s10434-013-3205-1

Clinical trial discussion, referral, and recruitment: Physician, patient, and system factors

Purpose Patient participation in cancer clinical trials is imperative to the advancement of medical science. Physicians play an important role in recruitment by discussing clinical trials with their cancer patients. Patient-physician discussion is influenced by many factors relating to the physician, the patient, and the healthcare system. Methods Physicians selected from the 2008-2009 American Medical Association Physician Masterfile who practiced in California, Florida, Illinois, or New York and specialized in medical oncology, surgery, or radiation oncology were surveyed about their attitudes and practices with respect to breast cancer clinical trials. Practice types were categorized according to the classifications provided by the American College of Surgeons, and clinical trial and practice addresses were geocoded. Results Surveys were completed by 706 of 1,534 eligible physicians (46 %). Medical oncologists were more likely than surgical or radiation oncologists to discuss the possibility, benefits, and risks of clinical trial enrollment with their breast cancer patients. Physicians who spent the most time in patient care were least likely to discuss clinical trials with their patients. Distance from a physician's practice to the nearest clinical trial site was inversely associated with referral and recruitment. Perceived barriers to clinical trial participation were associated with greater referral activity suggesting that physicians who were more involved in trials were also more likely to understand barriers to participation. Conclusions Multilevel interventions may be successful at increasing participation of women in clinical trials. © Springer Science+Business Media Dordrecht 2013.

Authors
Kaplan, CP; Nápoles, AM; Dohan, D; Hwang, ES; Melisko, M; Nickleach, D; Quinn, JA; Haas, J
MLA Citation
Kaplan, CP, Nápoles, AM, Dohan, D, Hwang, ES, Melisko, M, Nickleach, D, Quinn, JA, and Haas, J. "Clinical trial discussion, referral, and recruitment: Physician, patient, and system factors." Cancer Causes and Control 24.5 (2013): 979-988.
Source
scival
Published In
Cancer Causes & Control
Volume
24
Issue
5
Publish Date
2013
Start Page
979
End Page
988
DOI
10.1007/s10552-013-0173-5

Molecular profiling of human mammary gland links breast cancer risk to a p27+ cell population with progenitor characteristics

Early full-term pregnancy is one of the most effective natural protections against breast cancer. To investigate this effect, we have characterized the global gene expression and epigenetic profiles of multiple cell types from normal breast tissue of nulliparous and parous women and carriers of BRCA1 or BRCA2 mutations. We found significant differences in CD44+ progenitor cells, where the levels of many stem cell-related genes and pathways, including the cell-cycle regulator p27, are lower in parous women without BRCA1/BRCA2 mutations. We also noted a significant reduction in the frequency of CD44+p27+ cells in parous women and showed, using explant cultures, that parity-related signaling pathways play a role in regulating the number of p27+ cells and their proliferation. Our results suggest that pathways controlling p27+ mammary epithelial cells and the numbers of these cells relate to breast cancer risk and can be explored for cancer risk assessment and prevention. 2013 © 2013 Elsevier Inc.

Authors
Choudhury, S; Almendro, V; Merino, VF; Wu, Z; Maruyama, R; Su, Y; Martins, FC; Fackler, MJ; Bessarabova, M; Kowalczyk, A; Conway, T; Beresford-Smith, B; Macintyre, G; Cheng, Y-K; Lopez-Bujanda, Z; Kaspi, A; Hu, R; Robens, J; Nikolskaya, T; Haakensen, VD; Schnitt, SJ; Argani, P; Ethington, G; Panos, L; Grant, M; Clark, J; Herlihy, W; Lin, SJ; Chew, G; Thompson, EW; Greene-Colozzi, A; Richardson, AL; Rosson, GD; Pike, M; Garber, JE; Nikolsky, Y; Blum, JL; Au, A; Hwang, ES; Tamimi, RM; Michor, F et al.
MLA Citation
Choudhury, S, Almendro, V, Merino, VF, Wu, Z, Maruyama, R, Su, Y, Martins, FC, Fackler, MJ, Bessarabova, M, Kowalczyk, A, Conway, T, Beresford-Smith, B, Macintyre, G, Cheng, Y-K, Lopez-Bujanda, Z, Kaspi, A, Hu, R, Robens, J, Nikolskaya, T, Haakensen, VD, Schnitt, SJ, Argani, P, Ethington, G, Panos, L, Grant, M, Clark, J, Herlihy, W, Lin, SJ, Chew, G, Thompson, EW, Greene-Colozzi, A, Richardson, AL, Rosson, GD, Pike, M, Garber, JE, Nikolsky, Y, Blum, JL, Au, A, Hwang, ES, Tamimi, RM, and Michor, F et al. "Molecular profiling of human mammary gland links breast cancer risk to a p27+ cell population with progenitor characteristics." Cell Stem Cell 13.1 (2013): 117-130.
Source
scival
Published In
Cell Stem Cell
Volume
13
Issue
1
Publish Date
2013
Start Page
117
End Page
130
DOI
10.1016/j.stem.2013.05.004

Breast surgeon's survey: No consensus for surgical treatment of pleomorphic lobular carcinoma in situ

Authors
Blair, SL; Emerson, DK; Kulkarni, S; Hwang, ES; Malcarne, V; Ollila, DW
MLA Citation
Blair, SL, Emerson, DK, Kulkarni, S, Hwang, ES, Malcarne, V, and Ollila, DW. "Breast surgeon's survey: No consensus for surgical treatment of pleomorphic lobular carcinoma in situ." Breast Journal 19.1 (2013): 116-118.
Source
scival
Published In
The Breast Journal
Volume
19
Issue
1
Publish Date
2013
Start Page
116
End Page
118
DOI
10.1111/tbj.12062

Ductal carcinoma in situ (DCIS): Posttreatment follow-up care among Latina and non-Latina White women

Background: There is a lack of information about posttreatment care among patients with ductal carcinoma in situ (DCIS). This study compares posttreatment care by ethnicity-language and physician specialty among Latina and White women with DCIS. Methods: Latina and White women diagnosed with DCIS between 2002 and 2005 identified through the California Cancer Registry completed a telephone survey in 2006. Main outcomes were breast surveillance, lifestyle counseling, and follow-up physician specialty. Key results: Of 742 women (396 White, 349 Latinas), most (90 %) had at least one clinical breast exam (CBE). Among women treated with breast-conserving surgery (BCS; N = 503), 76 % had received at least two mammograms. While 92 % of all women had follow-up with a breast specialist, Spanish-speaking Latinas had the lowest specialist follow-up rates (84 %) of all groups. Lifestyle counseling was low with only 53 % discussing exercise, 43 % weight, and 31 % alcohol in relation to their DCIS. In multivariable analysis, Spanish-speaking Latinas with BCS had lower odds of receiving the recommended mammography screening in the year following treatment compared to Whites (OR 0. 5; 95 % CI, 0. 2-0. 9). Regardless of ethnicity-language, seeing both a specialist and primary care physician increased the odds of mammography screening and CBE (OR 1. 6; 95 % CI, 1. 2-2. 3 and OR 1. 9; 95 % CI, 1. 3-2. 8), as well as having discussions about exercise, weight, and alcohol use, compared to seeing a specialist only. Conclusions: Most women reported appropriate surveillance after DCIS treatment. However, our results suggest less adequate follow-up for Spanish-speaking Latinas, possibly due to language barriers or insurance access. Implications for Cancer Survivors: Follow-up with a primary care provider in addition to a breast specialist increases receipt of appropriate follow-up for all women. © 2013 Springer Science+Business Media New York.

Authors
López, ME; Kaplan, CP; Nápoles, AM; Livaudais, JC; Hwang, ES; Stewart, SL; Bloom, J; Karliner, L
MLA Citation
López, ME, Kaplan, CP, Nápoles, AM, Livaudais, JC, Hwang, ES, Stewart, SL, Bloom, J, and Karliner, L. "Ductal carcinoma in situ (DCIS): Posttreatment follow-up care among Latina and non-Latina White women." Journal of Cancer Survivorship 7.2 (2013): 219-226.
PMID
23408106
Source
scival
Published In
Journal of Cancer Survivorship
Volume
7
Issue
2
Publish Date
2013
Start Page
219
End Page
226
DOI
10.1007/s11764-012-0262-6

Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer: Translational Breast Cancer Research Consortium trial 017

BACKGROUND: Increased pathologic complete response (pCR) rates observed with neoadjuvant chemotherapy (NCT) for some subsets of patients with invasive breast cancer have prompted interest in whether patients who achieved a pCR can be identified preoperatively and potentially spared the morbidity of surgery. The objective of this multicenter, retrospective study was to estimate the accuracy of preoperative magnetic resonance imaging (MRI) in predicting a pCR in the breast. METHODS: MRI studies at baseline and after the completion of NCT plus data regarding pathologic response were collected retrospectively from 746 women who received treatment at 8 institutions between 2002 and 2011. Tumors were characterized by immunohistochemical phenotype into 4 categories based on receptor expression: hormone (estrogen and progesterone) receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 327), HR-positive/HER2-positive, (n = 148), HR-negative/HER2-positive, (n = 101), and triple-negative (HR-negative/HER2 negative; n = 155). In all, 194 of 249 patients (78%) with HER2-positive tumors received trastuzumab. Univariate and multivariate analyses of factors associated with radiographic complete response (rCR) and pCR were performed. RESULT: For the total group, the rCR and pCR rates were 182 of 746 patients (24%) and 179 of 746 patients (24%), respectively, and the highest pCR rate was observed for the triple-negative subtype (57 of 155 patients; 37%) and the HER2-positive subtype (38 of 101 patients; 38%). The overall accuracy of MRI for predicting pCR was 74%. The variables sensitivity, negative predictive value, positive predictive value, and accuracy differed significantly among tumor subtypes, and the greatest negative predictive value was observed in the triple-negative (60%) and HER2-positive (62%) subtypes. CONCLUSIONS: The overall accuracy of MRI for predicting pCR in invasive breast cancer patients who were receiving NCT was 74%. The performance of MRI differed between subtypes, possibly influenced by differences in pCR rates between groups. Future studies will determine whether MRI in combination with directed core biopsy improves the predictive value of MRI for pathologic response. Cancer 2013. © 2013 American Cancer Society.

Authors
Santos, JFDL; Cantor, A; Amos, KD; Forero, A; Golshan, M; Horton, JK; Hudis, CA; Hylton, NM; McGuire, K; Meric-Bernstam, F; Meszoely, IM; Nanda, R; Hwang, ES
MLA Citation
Santos, JFDL, Cantor, A, Amos, KD, Forero, A, Golshan, M, Horton, JK, Hudis, CA, Hylton, NM, McGuire, K, Meric-Bernstam, F, Meszoely, IM, Nanda, R, and Hwang, ES. "Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer: Translational Breast Cancer Research Consortium trial 017." Cancer 119.10 (2013): 1776-1783.
Source
scival
Published In
Cancer
Volume
119
Issue
10
Publish Date
2013
Start Page
1776
End Page
1783
DOI
10.1002/cncr.27995

Quality of life of Latina and Euro-American women with ductal carcinoma in situ

Background Risk factors for psychosocial distress following a breast cancer diagnosis include younger age, history of depression, inadequate social support, and serious comorbid conditions. Although these quality of life (QOL) concerns have been studied in women with ductal carcinoma in situ (DCIS), Latina women have been understudied. Methods Data were from a cross-sectional telephone survey of Latina and Euro-American women with DCIS recruited through a population-based cancer registry. The sample included 396 Euro-American women and 349 Latina women; 156 were interviewed in English and 193 in Spanish, with a median of 2 years after diagnosis. Regression models were created for measures in each of the following four QOL domains: physical, psychological, social, and spiritual. Results Younger age, no partner, and lower income were related to lower QOL in various domains. Physical comorbidities were associated with lower physical, psychological, and social QOL; lingering effects of surgery and prior depression were associated with lower QOL in all domains. English-speaking and Spanish-speaking Latinas (SSLs) reported higher spiritual QOL, and SSLs reported lower social QOL than Euro-American women. Conclusions Despite having lower mortality, women with DCIS are treated with surgery and radiation therapy as if they have invasive cancer, and the aftereffects of treatment can impact their QOL. SSLs are at risk for lower QOL partly because of poverty. However, Latinas' greater spiritual QOL may mitigate some of the psychological and social effects of treatment. Implications It is important to incorporate these findings into treatment decision making (choice of surgical treatment) and survivorship care (monitoring women with a history of depression or physical comorbidity). Copyright © 2012 John Wiley & Sons, Ltd.

Authors
Bloom, JR; Stewart, SL; Napoles, AM; Hwang, ES; Livaudais, JC; Karliner, L; Kaplan, CP
MLA Citation
Bloom, JR, Stewart, SL, Napoles, AM, Hwang, ES, Livaudais, JC, Karliner, L, and Kaplan, CP. "Quality of life of Latina and Euro-American women with ductal carcinoma in situ." Psycho-Oncology 22.5 (2013): 1008-1016.
Source
scival
Published In
Psycho-Oncology
Volume
22
Issue
5
Publish Date
2013
Start Page
1008
End Page
1016
DOI
10.1002/pon.3098

New treatment paradigms for patients with ductal carcinoma in situ

One of the most poorly understood clinical diagnoses in breast cancer is ductal carcinoma in situ (DCIS), which now accounts for almost one third of all mammographically detected malignancies. Detection and diagnosis of DCIS have improved, and mature data from randomized controlled trials of lumpectomy for DCIS have provided some measure of the magnitude of benefit to be derived from adjuvant treatments. The past 5 years have seen the emergence of molecular prognostic tools, which together with clinical factors have the potential to allow better selection of individualized therapies for these heterogeneous lesions. Ongoing and future research to identify which patients with DCIS can be safely managed with active surveillance are underway and will create opportunities to better understand the biology of this disease, thereby informing treatment strategies that are more closely aligned with the invasive potential of specific DCIS subtypes. © 2013 Springer Science+Business Media New York.

Authors
Mackey, A; Greenup, R; Hwang, ES
MLA Citation
Mackey, A, Greenup, R, and Hwang, ES. "New treatment paradigms for patients with ductal carcinoma in situ." Current Breast Cancer Reports 5.2 (2013): 86-98.
Source
scival
Published In
Current Breast Cancer Reports
Volume
5
Issue
2
Publish Date
2013
Start Page
86
End Page
98
DOI
10.1007/s12609-013-0109-9

FOXP3-positive regulatory T lymphocytes and epithelial FOXP3 expression in synchronous normal, ductal carcinoma in situ, and invasive cancer of the breast

FOXP3-expressing T regulatory lymphocytes (Tregs) have been described as putative mediators of immune tolerance, and thus facilitators of tumor growth. When found in association with various malignancies, Tregs are generally markers of poor clinical outcome. However, it is unknown whether they are also associated with cancer progression. We evaluated quantitative FOXP3 expression in lymphocytes as well as in epithelial cells in a set of thirty-two breast tumors with synchronous normal epithelium, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) components. Tumors were stained for FOXP3 and CD3 expression and Tregs quantified by determining the ratio of colocalized FOXP3 and CD3 relative to 1) total CD3-expressing lymphocytes and 2) to FOXP3-expressing epithelial cells. The median proportion of FOXP3-expressing CD3 cells significantly increased with malignant progression from normal to DCIS to IDC components (0.005, 0.019 and 0.030, respectively; p ≤ 0.0001 for normal vs. IDC and p = 0.004 for DCIS vs. IDC). The median intensity of epithelial FOXP3 expression was also increased with invasive progression and most markedly augmented between normal and DCIS components (0.130 vs. 0.175, p ≤ 0.0001). Both Treg infiltration and epithelial FOXP3 expression were higher in grade 3 vs. grade 1 tumors (p = 0.014 for Tregs, p = 0.038 for epithelial FOXP3), but did not vary significantly with hormone receptor status, size of invasive tumor, lymph node status, or disease stage. Notably, Treg infiltration significantly correlated with epithelial up-regulation of FOXP3 expression (p = 0.013 for normal, p = 0.001 for IDC). These findings implicate both Treg infiltration and up-regulated epithelial FOXP3 expression in breast cancer progression. © 2013 Springer Science+Business Media New York.

Authors
Lal, A; Chan, L; Devries, S; Chin, K; Scott, GK; Benz, CC; Chen, Y-Y; Waldman, FM; Hwang, ES
MLA Citation
Lal, A, Chan, L, Devries, S, Chin, K, Scott, GK, Benz, CC, Chen, Y-Y, Waldman, FM, and Hwang, ES. "FOXP3-positive regulatory T lymphocytes and epithelial FOXP3 expression in synchronous normal, ductal carcinoma in situ, and invasive cancer of the breast." Breast Cancer Research and Treatment 139.2 (2013): 381-390.
PMID
23712790
Source
scival
Published In
Breast Cancer Research and Treatment
Volume
139
Issue
2
Publish Date
2013
Start Page
381
End Page
390
DOI
10.1007/s10549-013-2556-4

Florid lobular carcinoma in situ: Molecular profiling and comparison to classic lobular carcinoma in situ and pleomorphic lobular carcinoma in situ

Summary We evaluated genomic alterations and biomarker expression in 20 florid lobular carcinomas in situ using array-based comparative genomic hybridization and immunohistochemical analysis. The genetic characteristics of florid lobular carcinoma in situ were compared with 20 classic lobular carcinomas in situ and 21 pleomorphic lobular carcinomas in situ (which included 8 apocrine variants), from our previously published data performed on a similar array-based comparative genomic hybridization platform. All 20 florid lobular carcinoma in situ cases were E-cadherin negative, and 92% were positive for estrogen receptor. Cyclin D1 expression correlated significantly negatively with estrogen receptor expression and was higher in cases with cyclin D1 (CCND1) gene amplification. Compared with classic lobular carcinoma in situ, florid lobular carcinoma in situ displayed significantly more fraction genome alteration (mean, 0.109 versus 0.072; P =.007), fraction genome loss (mean, 0.06 versus 0.03; P =.007), numbers of breakpoints (mean, 11.55 versus 6.95; P =.002), numbers of chromosome with breakpoints (mean, 5.85 versus 3.8; P =.004), and higher numbers of amplifications (mean, 2.10 versus 0.25; P =.03). Interestingly, florid lobular carcinoma in situ had the same genetic complexity as apocrine pleomorphic lobular carcinoma in situ. Our study demonstrated that florid lobular carcinoma in situ shares the cytologic features, E-cadherin loss, and the lobular genetic signature of 1q gain and 16q loss found in classic lobular carcinoma in situ. However, this variant demonstrates more genomic alterations than classic lobular carcinoma in situ and shares the same genetic complexity as apocrine pleomorphic lobular carcinoma in situ. Our data support the conclusion that florid lobular carcinoma in situ is genetically more advanced compared with the indolent phenotype of classic lobular carcinoma in situ. This may explain the greater frequency of concurrent invasive carcinoma in florid lobular carcinoma in situ compared with classic lobular carcinoma in situ. © 2013 Elsevier Inc.

Authors
Shin, SJ; Lal, A; Vries, SD; Suzuki, J; Roy, R; Hwang, ES; Schnitt, SJ; Waldman, FM; Chen, Y-Y
MLA Citation
Shin, SJ, Lal, A, Vries, SD, Suzuki, J, Roy, R, Hwang, ES, Schnitt, SJ, Waldman, FM, and Chen, Y-Y. "Florid lobular carcinoma in situ: Molecular profiling and comparison to classic lobular carcinoma in situ and pleomorphic lobular carcinoma in situ." Human Pathology 44.10 (2013): 1998-2009.
Source
scival
Published In
Human Pathology
Volume
44
Issue
10
Publish Date
2013
Start Page
1998
End Page
2009
DOI
10.1016/j.humpath.2013.04.004

Abstract P4-14-04: Total skin-sparing mastectomy in BRCA mutation carriers

Authors
Warren, PA; Hwang, ES; Ewing, CA; Alvarado, M; Esserman, LJ
MLA Citation
Warren, PA, Hwang, ES, Ewing, CA, Alvarado, M, and Esserman, LJ. "Abstract P4-14-04: Total skin-sparing mastectomy in BRCA mutation carriers." Cancer Research 72.24 Supplement (December 15, 2012): P4-14-04-P4-14-04.
Source
crossref
Published In
Cancer Research
Volume
72
Issue
24 Supplement
Publish Date
2012
Start Page
P4-14-04
End Page
P4-14-04
DOI
10.1158/0008-5472.SABCS12-P4-14-04

Abstract P4-16-07: Selective use of post-mastectomy radiation therapy in the neoadjuvant setting

Authors
Warren, PA; Wang, F; Stover, AC; Rugo, HS; Melisko, ME; Park, JW; Alvarado, M; Ewing, CA; Esserman, LJ; Fowble, B; Hwang, ES
MLA Citation
Warren, PA, Wang, F, Stover, AC, Rugo, HS, Melisko, ME, Park, JW, Alvarado, M, Ewing, CA, Esserman, LJ, Fowble, B, and Hwang, ES. "Abstract P4-16-07: Selective use of post-mastectomy radiation therapy in the neoadjuvant setting." Cancer Research 72.24 Supplement (December 15, 2012): P4-16-07-P4-16-07.
Source
crossref
Published In
Cancer Research
Volume
72
Issue
24 Supplement
Publish Date
2012
Start Page
P4-16-07
End Page
P4-16-07
DOI
10.1158/0008-5472.SABCS12-P4-16-07

Extra-cellular Matrix Stiffness and Immune Cells Infiltrate Are Associated With Breast Tumor Phenotype

Authors
Acerbi, I; Zheng, SY; Ruffell, B; Au, A; Shi, Q; Liphardt, JT; Coussens, LM; Chen, YY; Hwang, ES; Weaver, VM
MLA Citation
Acerbi, I, Zheng, SY, Ruffell, B, Au, A, Shi, Q, Liphardt, JT, Coussens, LM, Chen, YY, Hwang, ES, and Weaver, VM. "Extra-cellular Matrix Stiffness and Immune Cells Infiltrate Are Associated With Breast Tumor Phenotype." July 2012.
Source
wos-lite
Published In
European Journal of Cancer
Volume
48
Publish Date
2012
Start Page
S91
End Page
S91

Reframing treatment for ductal carcinoma in situ: could less be more?

Authors
Hwang, ES; Nelson, H
MLA Citation
Hwang, ES, and Nelson, H. "Reframing treatment for ductal carcinoma in situ: could less be more?." Bull Am Coll Surg 97.6 (June 2012): 50-51.
PMID
22745990
Source
pubmed
Published In
Bulletin of the American College of Surgeons
Volume
97
Issue
6
Publish Date
2012
Start Page
50
End Page
51

Cell-extrinsic consequences of epithelial stress: Activation of protumorigenic tissue phenotypes

Introduction: Tumors are characterized by alterations in the epithelial and stromal compartments, which both contribute to tumor promotion. However, where, when, and how the tumor stroma develops is still poorly understood. We previously demonstrated that DNA damage or telomere malfunction induces an activin A-dependent epithelial stress response that activates cell-intrinsic and cell-extrinsic consequences in mortal, nontumorigenic human mammary epithelial cells (HMECs and vHMECs). Here we show that this epithelial stress response also induces protumorigenic phenotypes in neighboring primary fibroblasts, recapitulating many of the characteristics associated with formation of the tumor stroma (for example, desmoplasia).Methods: The contribution of extrinsic and intrinsic DNA damage to acquisition of desmoplastic phenotypes was investigated in primary human mammary fibroblasts (HMFs) co-cultured with vHMECs with telomere malfunction (TRF2-vHMEC) or in HMFs directly treated with DNA-damaging agents, respectively. Fibroblast reprogramming was assessed by monitoring increases in levels of selected protumorigenic molecules with quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and immunocytochemistry. Dependence of the induced phenotypes on activin A was evaluated by addition of exogenous activin A or activin A silencing. In vitro findings were validated in vivo, in preinvasive ductal carcinoma in situ (DCIS) lesions by using immunohistochemistry and telomere-specific fluorescent in situ hybridization.Results: HMFs either cocultured with TRF2-vHMEC or directly exposed to exogenous activin A or PGE2 show increased expression of cytokines and growth factors, deposition of extracellular matrix (ECM) proteins, and a shift toward aerobic glycolysis. In turn, these "activated" fibroblasts secrete factors that promote epithelial cell motility. Interestingly, cell-intrinsic DNA damage in HMFs induces some, but not all, of the molecules induced as a consequence of cell-extrinsic DNA damage. The response to cell-extrinsic DNA damage characterized in vitro is recapitulated in vivo in DCIS lesions, which exhibit telomere loss, heightened DNA damage response, and increased activin A and cyclooxygenase-2 expression. These lesions are surrounded by a stroma characterized by increased expression of α smooth muscle actin and endothelial and immune cell infiltration.Conclusions: Thus, synergy between stromal and epithelial interactions, even at the initiating stages of carcinogenesis, appears necessary for the acquisition of malignancy and provides novel insights into where, when, and how the tumor stroma develops, allowing new therapeutic strategies. © 2012 Fordyce et al.; licensee BioMed Central Ltd.

Authors
Fordyce, CA; Patten, KT; Fessenden, TB; DeFilippis, R; Hwang, ES; Zhao, J; Tlsty, TD
MLA Citation
Fordyce, CA, Patten, KT, Fessenden, TB, DeFilippis, R, Hwang, ES, Zhao, J, and Tlsty, TD. "Cell-extrinsic consequences of epithelial stress: Activation of protumorigenic tissue phenotypes." Breast Cancer Research 14.6 (2012).
PMID
23216814
Source
scival
Published In
Breast Cancer Research
Volume
14
Issue
6
Publish Date
2012
DOI
10.1186/bcr3368

Paget's disease of the breast masquerading as squamous cell carcinoma on cytology: A case report

Paget's disease is an uncommon manifestation of breast carcinoma occurring in 1-2% of female patients with breast cancer. Here, we present a case of Paget's disease of the breast, which was initially interpreted as squamous cell carcinoma on cytology. This case report raises two issues. First, histological and cytological specimens of Paget's disease show a mixed population of epithelial cells including squamous cells with reactive changes and malignant glandular cells. In the current case, a mixed population of atypical keratinizing and nonkeratinizing epithelial cells was initially interpreted as squamous cell carcinoma of cutaneous origin. The marked reactive changes in the squamous epithelium involved by Paget's disease should be recognized. Second, this case is an unusual clinical presentation for Paget's disease of the breast as the nipple-areolar complex and underlying breast tissue were surgically absent at the time of diagnosis. Clinical suspicion, along with an awareness of the cytologic features and clinical presentation of Paget's disease, can help in reaching the correct diagnosis in a timely fashion. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.

Authors
Vohra, P; Ljung, B-ME; Miller, TR; Hwang, E-S; Zante, AV
MLA Citation
Vohra, P, Ljung, B-ME, Miller, TR, Hwang, E-S, and Zante, AV. "Paget's disease of the breast masquerading as squamous cell carcinoma on cytology: A case report." Diagnostic Cytopathology 40.11 (2012): 1015-1018.
PMID
21548119
Source
scival
Published In
Diagnostic Cytopathology
Volume
40
Issue
11
Publish Date
2012
Start Page
1015
End Page
1018
DOI
10.1002/dc.21712

Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer

Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene expression, and imaging features, and by comparing NAC response rates to those seen in IDC after adjustment for these factors. We combined datasets from two large prospective NAC trials, including in total 676 patients, of which 75 were of lobular histology. Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes, and underwent serial biopsies, expression microarray analysis, and MRI imaging. We compared pathologic complete response (pCR) rates and breast conservation surgery (BCS) rates between ILC and IDC, adjusted for clinicopathologic factors. On univariate analysis, ILCs were significantly less likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the known differences in tumor characteristics between the two histologic types, including hormone receptor (HR) status, HER2 status, histological grade, and p53 expression, accounted for this difference with the lowest pCR rates among HR+/HER2- tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR- and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI 70-gene signature, was correlated with pCR, although the small numbers of ILC in each group precluded significant associations. BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics. We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC. However, this difference is explained by differences in molecular characteristics, particularly HR and HER2, and independent of lobular histology. © 2012 Springer Science+Business Media, LLC.

Authors
Lips, EH; Mukhtar, RA; Yau, C; Ronde, JJD; Livasy, C; Carey, LA; Loo, CE; Vrancken-Peeters, M-JTFD; Sonke, GS; Berry, DA; Veer, LJV; Esserman, LJ; Wesseling, J; Rodenhuis, S; Hwang, ES
MLA Citation
Lips, EH, Mukhtar, RA, Yau, C, Ronde, JJD, Livasy, C, Carey, LA, Loo, CE, Vrancken-Peeters, M-JTFD, Sonke, GS, Berry, DA, Veer, LJV, Esserman, LJ, Wesseling, J, Rodenhuis, S, and Hwang, ES. "Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer." Breast Cancer Research and Treatment 136.1 (2012): 35-43.
PMID
22961065
Source
scival
Published In
Breast Cancer Research and Treatment
Volume
136
Issue
1
Publish Date
2012
Start Page
35
End Page
43
DOI
10.1007/s10549-012-2233-z

Outcomes after total skin-sparing mastectomy and immediate reconstruction in 657 breasts

Background. Total skin-sparing mastectomy (TSSM), a technique comprising removal of all breast and nipple tissue while preserving the entire skin envelope, is increasingly offered to women for therapeutic and prophylactic indications. However, standard use of the procedure remains controversial as a result oft concerns regarding oncologic safety and risk of complications. Methods. Outcomes from a prospectively maintained database of patients undergoing TSSM and immediate breast reconstruction from 2001 to 2010 were reviewed. Outcome measures included postoperative complications, tumor involvement of the nipple-areolar complex (NAC) on pathologic analysis, and cancer recurrence. Results. TSSM was performed on 657 breasts in 428 patients. Indications included in situ cancer [111 breasts (16.9 %)], invasive cancer [301 breasts (45.8 %)], and prophylactic risk-reduction [245 breasts (37.3 %)]. A total of 210 patients (49 %) had neoadjuvant chemotherapy, 78 (18.2 %) had adjuvant chemotherapy, and 114 (26.7 %) had postmastectomy radiotherapy. Nipple tissue contained in situ cancer in 11 breasts (1.7 %) and invasive cancer in 9 breasts (1.4 %); management included repeat excision (7 cases), NAC removal (9 cases), or radiotherapy without further excision (4 cases). Ischemic complications included 13 cases (2 %) of partial nipple loss, 10 cases (1.5 %) of complete nipple loss, and 78 cases (11.9 %) of skin flap necrosis. Overall locoregional recurrence rate was 2 % (median follow-up 28 months), with a 2.4 % rate observed in the subset of patients with at least 3 years' follow-up (median 45 months). No NAC skin recurrences were observed. Conclusions. In this large, high-risk cohort, TSSM was associated with low rates of NAC complications, nipple involvement, and locoregional recurrence. © Society of Surgical Oncology 2012.

Authors
Peled, AW; Foster, RD; Stover, AC; Itakura, K; Ewing, CA; Alvarado, M; Hwang, ES; Esserman, LJ
MLA Citation
Peled, AW, Foster, RD, Stover, AC, Itakura, K, Ewing, CA, Alvarado, M, Hwang, ES, and Esserman, LJ. "Outcomes after total skin-sparing mastectomy and immediate reconstruction in 657 breasts." Annals of Surgical Oncology 19.11 (2012): 3402-3409.
PMID
22526909
Source
scival
Published In
Annals of Surgical Oncology
Volume
19
Issue
11
Publish Date
2012
Start Page
3402
End Page
3409
DOI
10.1245/s10434-012-2362-y

Increasing the time to expander-implant exchange after postmastectomy radiation therapy reduces expander-implant failure

Background: Increased rates of complications can occur when postmastectomy radiation therapy is required after immediate expander-implant breast reconstruction. The sequence and timing of tissue expansion and implant exchange with regard to postmastectomy radiation therapy may impact complication rates. Methods: A prospectively maintained database of patients undergoing mastectomy and immediate reconstruction was queried for patients who underwent postmastectomy radiation therapy. The authors protocol is to complete tissue expansion before radiation, irradiate the fully inflated expander, and then perform expander-implant exchange. Starting in 2009, the authors refined their protocol by increasing the time interval between completion of radiation therapy and expander-implant exchange from 3 months to 6 months as a strategy to reduce surgical complications. For analysis, patients were divided into two cohorts based on whether expander-implant exchange was performed less than 6 months or more than 6 months after radiation. The primary outcome was expander-implant failure, defined as device removal without concurrent replacement. Results: Eighty-eight patients met selection criteria; 49 (55.7 percent) had expander-implant exchange within 6 months of completing radiation therapy (mean, 3.4 months; range, 1.2 to 5.8 months), and the rest had at least a 6-month interval (mean, 8.6 months; range, 6.1 to 17.1 months). Risk factors for postoperative complications were equivalent between cohorts. Overall expander-implant failure was 15.9 percent; failure was significantly higher in the cohort with less than 6 months time before exchange (22.4 percent versus 7.7 percent, p = 0.036). CONCLUSION:: Delaying expander-implant exchange for at least 6 months after the completion of postmastectomy radiation therapy can significantly reduce expander-implant failure. Clinical Question/Level of Evidence: Therapeutic, III. © 2012 by the American Society of Plastic Surgeons.

Authors
Peled, AW; Foster, RD; Esserman, LJ; Park, CC; Hwang, ES; Fowble, B
MLA Citation
Peled, AW, Foster, RD, Esserman, LJ, Park, CC, Hwang, ES, and Fowble, B. "Increasing the time to expander-implant exchange after postmastectomy radiation therapy reduces expander-implant failure." Plastic and Reconstructive Surgery 130.3 (2012): 503-509.
PMID
22929235
Source
scival
Published In
Plastic and Reconstructive Surgery
Volume
130
Issue
3
Publish Date
2012
Start Page
503
End Page
509
DOI
10.1097/PRS.0b013e31825dbf15

Evaluating the feasibility of extended partial mastectomy and immediate reduction mammoplasty reconstruction as an alternative to mastectomy

Objectives: To assess the efficacy of using concurrent partial mastectomy and reduction mammoplasty for resection of a wide range of tumor sizes and compare oncologic outcomes and postoperative complications on the basis of tumor size. Background: Although tumor size greater than 4 cm has been considered an indication for undergoing a mastectomy, this dictum may not apply in women with breast hypertrophy, where the ratio of tumor size to breast size may still permit breast conservation. We wished to evaluate whether an approach combining partial mastectomy with reduction mammoplasty could provide a safe oncologic procedure with immediate breast reconstruction that could technically be applied even for large (>4 cm) lesions. Methods: A retrospective review of all patients undergoing partial mastectomy and concurrent reduction mammoplasty performed at our institution from 2000 to 2009. Clinical characteristics at presentation, pathologic data, and follow-up data were collected and analyzed. Results: Eighty-five consecutive simultaneous partial mastectomy/reduction mammoplasty procedures were performed in 79 patients. Average tumor size was 2.8 cm for ductal carcinoma in situ (0.05-17.0 cm), 2.4 cm for invasive ductal carcinoma (IDC) (0.2-8.9 cm), 3.5 cm for lobular carcinoma (1.6-8.0 cm), and 5.7 cm for phyllodes tumors (3.7-7.6 cm). Twenty-five of 85 tumors (29.4%) were larger than 4 cm. Distribution for stage 0, I, II, III, and IV disease was 15, 12, 35, 19, and 2 tumors respectively, with an additional 2 phyllodes tumors. Median follow-up was 39 months (10-130 months). Seventy-five patients (94.9%) achieved successful breast conservation, whereas 4 patients (5.1%) went on to completion mastectomy. Thirteen patients (16.4%) required 1 reexcision to achieve clear margins, and 2 (2.5%) required multiple reexcisions. Two patients had a local recurrence during the follow-up period, one of whom underwent reexcision and the other underwent mastectomy. The overall complication rate was 14.1%, which included 4 major complications (4.7%) requiring an unplanned return to the operating room and need for hospital readmission, and 8 minor wound-related complications (9.4%). Neither recurrence nor complication rates were increased in patients with tumors greater than 4 cm when compared with tumors less than or equal to 4 cm. Conclusions: A partial mastectomy with concurrent reduction mammoplasty technique is a viable option for breast conservation even for larger tumors, combining a safe oncologic procedure with excellent cosmesis. A combined effort between breast surgeons and reconstructive surgeons has a high probability of success with low recurrence rates. In carefully selected patients, this approach may be preferable to mastecomy and breast reconstruction, particularly when postmastectomy radiation therapy is anticipated. © 2012 by Lippincott Williams & Wilkins.

Authors
Chang, EI; Peled, AW; Foster, RD; Lin, C; Zeidler, KR; Ewing, CA; Alvarado, M; Hwang, ES; Esserman, LJ
MLA Citation
Chang, EI, Peled, AW, Foster, RD, Lin, C, Zeidler, KR, Ewing, CA, Alvarado, M, Hwang, ES, and Esserman, LJ. "Evaluating the feasibility of extended partial mastectomy and immediate reduction mammoplasty reconstruction as an alternative to mastectomy." Annals of Surgery 255.6 (2012): 1151-1157.
PMID
22470069
Source
scival
Published In
Annals of Surgery
Volume
255
Issue
6
Publish Date
2012
Start Page
1151
End Page
1157
DOI
10.1097/SLA.0b013e31824f9769

The effects of acellular dermal matrix in expander-implant breast reconstruction after total skin-sparing mastectomy: Results of a prospective practice improvement study

Background: Neither outcome after total skin-sparing mastectomy and expander-implant reconstruction using acellular dermal matrix nor a strategy for optimal acellular dermal matrix selection criteria has been well described. Methods: Prospective review of three patient cohorts undergoing total skin-sparing mastectomy with preservation of the nipple-areola complex and immediate expander-implant reconstruction from 2006 to 2010 was performed. Cohort 1 (no acellular dermal matrix) comprised 90 cases in which acellular dermal matrix was not used. Cohort 2 (consecutive acellular dermal matrix) included the next 100 consecutive cases, which all received acellular dermal matrix. Cohort 3 (selective acellular dermal matrix) consisted of the next 260 cases, in which acellular dermal matrix was selectively used based on mastectomy skin flap thickness. Complication rates were compared using chi-square analysis. Results: The study included 450 cases in 288 patients. Mean follow-up was 25.5 months. Infection occurred in 27.8 percent of the no-acellular dermal matrix cases, 20 percent of the consecutive cases, and 15.8 percent of the selective cases (p = 0.04). Unplanned return to the operating room was required in 23.3, 11, and 10 percent of cases, respectively (p = 0.004). Expander-implant loss occurred in 17.8, 7, and 5 percent of cases, respectively (p = 0.001). Additional analysis of the odds ratios of developing complications after postmastectomy radiation therapy demonstrated a specific protective benefit of acellular dermal matrix in irradiated patients. Conclusions: Acellular dermal matrix use in expander-implant reconstruction after total skin-sparing mastectomy reduced major postoperative complications in this study. Maximal benefit is achieved with selected use in patients with thin mastectomy skin flaps and those receiving radiation therapy. Copyright © 2012 by the American Society of Plastic Surgeons.

Authors
Peled, AW; Foster, RD; Garwood, ER; Moore, DH; Ewing, CA; Alvarado, M; Hwang, ES; Esserman, LJ
MLA Citation
Peled, AW, Foster, RD, Garwood, ER, Moore, DH, Ewing, CA, Alvarado, M, Hwang, ES, and Esserman, LJ. "The effects of acellular dermal matrix in expander-implant breast reconstruction after total skin-sparing mastectomy: Results of a prospective practice improvement study." Plastic and Reconstructive Surgery 129.6 (2012): 901e-908e.
PMID
22634688
Source
scival
Published In
Plastic and Reconstructive Surgery
Volume
129
Issue
6
Publish Date
2012
Start Page
901e
End Page
908e
DOI
10.1097/PRS.0b013e31824ec447

Role of postmastectomy radiation after neoadjuvant chemotherapy in stage II-III breast cancer

Purpose: To identify a cohort of women treated with neoadjuvant chemotherapy and mastectomy for whom postmastectomy radiation therapy (PMRT) may be omitted according to the projected risk of local-regional failure (LRF). Methods and Materials: Seven breast cancer physicians from the University of California cancer centers created 14 hypothetical clinical case scenarios, identified, reviewed, and abstracted the available literature (MEDLINE and Cochrane databases), and formulated evidence tables with endpoints of LRF, disease-free survival, and overall survival. Using the American College of Radiology appropriateness criteria methodology, appropriateness ratings for postmastectomy radiation were assigned for each scenario. Finally, an overall summary risk assessment table was developed. Results: Of 24 sources identified, 23 were retrospective studies from single institutions. Consensus on the appropriateness rating, defined as 80% agreement in a category, was achieved for 86% of the cases. Distinct LRF risk categories emerged. Clinical stage II (T1-2N0-1) patients, aged >40 years, estrogen receptor-positive subtype, with pathologic complete response or 0-3 positive nodes without lymphovascular invasion or extracapsular extension, were identified as having ≤10% risk of LRF without radiation. Limited data support stage IIIA patients with pathologic complete response as being low risk. Conclusions: In the absence of randomized trial results, existing data can be used to guide the use of PMRT in the neoadjuvant chemotherapy setting. Using available studies to inform appropriateness ratings for clinical scenarios, we found a high concordance of treatment recommendations for PMRT and were able to identify a cohort of women with a low risk of LRF without radiation. These low-risk patients will form the basis for future planned studies within the University of California Athena Breast Health Network. © 2012 Elsevier Inc. All rights reserved.

Authors
Fowble, BL; Einck, JP; Kim, DN; McCloskey, S; Mayadev, J; Yashar, C; Chen, SL; Hwang, ES
MLA Citation
Fowble, BL, Einck, JP, Kim, DN, McCloskey, S, Mayadev, J, Yashar, C, Chen, SL, and Hwang, ES. "Role of postmastectomy radiation after neoadjuvant chemotherapy in stage II-III breast cancer." International Journal of Radiation Oncology Biology Physics 83.2 (2012): 494-503.
PMID
22579377
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
83
Issue
2
Publish Date
2012
Start Page
494
End Page
503
DOI
10.1016/j.ijrobp.2012.01.068

Long-term reconstructive outcomes after expander-implant breast reconstruction with serious infectious or wound-healing complications

INTRODUCTION: Immediate expander-implant breast reconstruction has been associated with postoperative complications, including infection and wound-healing problems. In extreme cases, these issues can lead to expander-implant loss. Little is known about the long-term reconstructive outcomes for patients who develop major complications threatening their expander-implant reconstructions. METHODS: A review of all patients who underwent mastectomy and immediate expander-implant reconstruction at University of California, San Francisco (UCSF) from 2005 to 2007 was performed. A prospective database was queried for patients who developed a major postoperative complication related to infection or wound-healing problems requiring unplanned operative intervention. Only patients who had a minimum of 3 years' follow-up were included in the study. RESULTS: Twenty-nine patients were identified who met study criteria. Mean follow-up time was 52.5 months (range, 41-71 months). Six of the 29 (20.7%) patients had received prior breast irradiation, and 9 patients (31%) underwent postoperative radiation therapy. Reasons for unplanned return to the operating room included infection (n = 11, 37.9%), expander-implant exposure (n = 5, 17.2%), nonhealing wounds without underlying exposure (n = 3, 1.3%), or >1 of these indications (n = 10, 34.5%). Unplanned operative intervention (such as wound debridement or expander-implant exchange or removal) was required once in 10 patients (34.5%), twice in 10 patients (34.5%), 3 times in 4 patients (13.8%), 4 times in 1 patient (3.4%), and 5 or greater times in 4 patients (13.8%). At the conclusion of all operative interventions, 15 patients (51.7%) had successful breast reconstruction using an expander-implant technique. Five additional patients (17.3%) ultimately achieved successful salvage reconstruction with either a transverse rectus abdominis myocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flap. Nine patients (31%) did not have successful breast reconstruction. Of these 9 patients, 5 elected to abandon reconstructive efforts after 1 unplanned return to the operating room for expander-implant removal, whereas the rest underwent at least 1 attempt at expander-implant salvage, with the overall rate of final successful reconstruction after attempt at salvage 83.3% (20 of 24 patients). CONCLUSIONS: Even when unplanned operative intervention is required to address postoperative wound-healing or infectious complications after expander-implant reconstruction, the majority of patients can achieve successful reconstructive outcomes at long-term follow-up, including those patients requiring multiple operative interventions to treat their complication. Copyright © 2012 by Lippincott Williams & Wilkins.

Authors
Peled, AW; Stover, AC; Foster, RD; McGrath, MH; Hwang, ES
MLA Citation
Peled, AW, Stover, AC, Foster, RD, McGrath, MH, and Hwang, ES. "Long-term reconstructive outcomes after expander-implant breast reconstruction with serious infectious or wound-healing complications." Annals of Plastic Surgery 68.4 (2012): 369-373.
PMID
22421481
Source
scival
Published In
Annals of Plastic Surgery
Volume
68
Issue
4
Publish Date
2012
Start Page
369
End Page
373
DOI
10.1097/SAP.0b013e31823aee67

Leukocyte composition of human breast cancer

Retrospective clinical studies have used immune-based biomarkers, alone or in combination, to predict survival outcomes for women with breast cancer (BC); however, the limitations inherent to immunohistochemical analyses prevent comprehensive descriptions of leukocytic infiltrates, as well as evaluation of the functional state of leukocytes in BC stroma. To more fully evaluate this complexity, and to gain insight into immune responses after chemotherapy (CTX), we prospectively evaluated tumor and nonadjacent normal breast tissue from women with BC, who either had or had not received neoadjuvant CTX before surgery. Tissues were evaluated by polychromatic flow cytometry in combination with confocal immunofluorescence and immunohistochemical analysis of tissue sections. These studies revealed that activated T lymphocytes predominate in tumor tissue, whereas myeloid lineage cells are more prominant in "normal" breast tissue. Notably, residual tumors from an unselected group of BC patients treated with neoadjuvant CTX contained increased percentages of infiltrating myeloid cells, accompanied by an increased CD8/CD4T-cell ratio and higher numbers of granzyme B-expressing cells, compared with tumors removed from patients treated primarily by surgery alone. These data provide an initial evaluation of differences in the immune microenvironment of BC compared with nonadjacent normal tissue and reveal the degree to which CTX may alter the complexity and presence of selective subsets of immune cells in tumors previously treated in the neoadjuvant setting.

Authors
Ruffell, B; Au, A; Rugo, HS; Esserman, LJ; Hwang, ES; Coussens, LM
MLA Citation
Ruffell, B, Au, A, Rugo, HS, Esserman, LJ, Hwang, ES, and Coussens, LM. "Leukocyte composition of human breast cancer." Proceedings of the National Academy of Sciences of the United States of America 109.8 (2012): 2796-2801.
PMID
21825174
Source
scival
Published In
Proceedings of the National Academy of Sciences of USA
Volume
109
Issue
8
Publish Date
2012
Start Page
2796
End Page
2801
DOI
10.1073/pnas.1104303108

Adjuvant hormonal therapy use among women with ductal carcinoma in situ

Objective: In the absence of consistent guidelines for the use of adjuvant hormonal therapy (HT) in treating ductal carcinoma in situ (DCIS), our purpose was to explore a variety of factors associated with discussion, use, and discontinuation of this therapy for DCIS, including patient, tumor, and treatment-related characteristics and physician-patient communication factors. Methods: We identified women from eight California Cancer Registry regions diagnosed with DCIS from 2002 through 2005, aged ≥18 years, of Latina or non-Latina white race/ethnicity. A total of 744 women were interviewed an average of 24 months postdiagnosis about whether they had (1) discussed with a physician, (2) used, and (3) discontinued adjuvant HT. Results: Although 83% of women discussed adjuvant HT with a physician, 47% used adjuvant HT, and 23% of users reported discontinuation by a median of 11 months. In multivariable adjusted analyses, Latina Spanish speakers were less likely than white women to discuss therapy (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.18-0.69) and more likely to discontinue therapy (OR 2.67, 95% CI 1.05-6.81). Seeing an oncologist for follow-up care was associated with discussion (OR 5.10, 95% CI 3.14-8.28) and use of therapy (OR 4.20, 95% CI 2.05-8.61). Similarly, physician recommendation that treatment was necessary vs. optional was positively associated with use (OR 11.2, 95% CI 6.50-19.4) and inversely associated with discontinuation (OR 0.38, 95% CI 0.19-0.73). Conclusions: Physician recommendation is an important factor associated with use and discontinuation of adjuvant HT for DCIS. Differences in discussion and discontinuation of therapy according to patient characteristics, particularly ethnicity/language, suggest challenges to physician-patient communication about adjuvant HT across a language barrier. © Copyright 2012, Mary Ann Liebert, Inc. 2012.

Authors
Livaudais, JC; Hwang, ES; Karliner, L; Nápoles, A; Stewart, S; Bloom, J; Kaplan, CP
MLA Citation
Livaudais, JC, Hwang, ES, Karliner, L, Nápoles, A, Stewart, S, Bloom, J, and Kaplan, CP. "Adjuvant hormonal therapy use among women with ductal carcinoma in situ." Journal of Women's Health 21.1 (2012): 35-42.
PMID
21902542
Source
scival
Published In
Journal of Women's Health
Volume
21
Issue
1
Publish Date
2012
Start Page
35
End Page
42
DOI
10.1089/jwh.2011.2773

Neoadjuvant endocrine therapy in the treatment of early-stage breast cancer

Endocrine therapy is the first targeted biologic therapy to be used in breast cancer treatment and was initially conceived in 1895. Based on the observation that lactation led to a cancer-like ductal epithelial proliferation in cattle and that castration of these cattle led to fatty degeneration of this epithelium, George Thomas Beatson, a Scottish surgeon, hypothesized that bilateral oophorectomy might benefit women with advanced breast cancer. He tested this hypothesis in Glasgow Cancer Hospital on a 33-year-old woman with recurrent soft tissue, axillary, and chest wall disease. Beatson described the case in the Lancet in 1896, reporting significant regression of the patient's cancer after which she survived for another 4 years. Beatson's initial report and subsequent reasoning in a 1901 edition of the Lancet that, "we must look in the female to the ovaries as the seat of the exciting cause of carcinoma, certainly of the mamma.." led to the adoption of oophorectomy for breast cancer. Although oophorectomy was effective in only about a third of women with advanced breast cancer, it became the standard of care for patients with limited adjuvant treatment options. This chapter provides an overview of available endocrine options for neoadjuvant therapy of breast cancer. © 2011 Springer Science + Business Media.

Authors
Hwang, ES; Jelin, E
MLA Citation
Hwang, ES, and Jelin, E. "Neoadjuvant endocrine therapy in the treatment of early-stage breast cancer." 2011. 717-729.
Source
scival
Publish Date
2011
Start Page
717
End Page
729
DOI
10.1007/978-1-4419-6076-4_59

Outcome of long term active surveillance for estrogen receptor-positive ductal carcinoma in situ

Introduction: An option for active surveillance is not currently offered to patients with ductal carcinoma in situ (DCIS); however a small number of women decline standard surgical treatment for noninvasive cancer. The purpose of this study was to assess outcomes in a cohort of 14 well-informed women who elected non-surgical active surveillance with endocrine treatment alone for estrogen receptor-positive DCIS. Methods: Retrospective review of 14 women, 12 of whom were enrolled in an IRB-approved single-arm study of 3 months of neoadjuvant endocrine therapy prior to definitive surgical management. The patients in this report withdrew from the parent study opting instead for active surveillance with endocrine treatment and imaging. Results: 8 women had surgery at a median follow up of 28.3 months (range 10.1-70 months), 5 had stage I IDC at surgical excision, and 3 had DCIS alone. 6 women remain on surveillance without evidence of invasive disease for a median of 31.8 months (range 11.8-80.8 months). Conclusion: Long-term active surveillance for DCIS is feasible in a well-informed patient population, but is associated with risk of invasive cancer at surgical excision. © 2011 Elsevier Ltd.

Authors
Meyerson, AF; Lessing, JN; Itakura, K; Hylton, NM; Wolverton, DE; Joe, BN; Esserman, LJ; Hwang, ES
MLA Citation
Meyerson, AF, Lessing, JN, Itakura, K, Hylton, NM, Wolverton, DE, Joe, BN, Esserman, LJ, and Hwang, ES. "Outcome of long term active surveillance for estrogen receptor-positive ductal carcinoma in situ." Breast 20.6 (2011): 529-533.
PMID
21843942
Source
scival
Published In
The Breast
Volume
20
Issue
6
Publish Date
2011
Start Page
529
End Page
533
DOI
10.1016/j.breast.2011.06.001

Genomic alterations and phenotype of large compared to small high-grade ductal carcinoma in situ

A clinically distinct subgroup of pure ductal carcinoma in situ presents as an extensive, high-grade lesion, which nevertheless lacks invasion. We sought to evaluate differences between those ductal carcinomas in situ presenting as large versus small lesions while controlling for high-grade, to determine whether there exist phenotypic and genetic differences between the 2 groups. Fifty-two cases of pure high-grade ductal carcinomas in situ were collected retrospectively, consisting of 27 large (>40 mm) and 25 small (<15 mm) cases. The 2 groups were compared based on genomic copy number assessed by array-based comparative genomic hybridization and by phenotype determined by immunohistochemistry for estrogen receptor, progesterone receptor, Ki-67, p53, cyclin D1, p16, cyclooxygenase 2, human epidermal growth factor receptor 2, and CD68. Large lesions presented at a younger age, with lower incidence of comedonecrosis and periductal macrophage response. Larger lesions also had significantly lower estrogen receptor expression, lower cyclin D1 expression, and lower Ki-67 index. The subset of 9 large palpable tumors had significantly lower p16/cyclooxygenase 2 expression and lower Ki-67 index compared to nonpalpable tumors. Genomically, larger lesions had fewer break points, fewer amplifications, and decreased copy number gains involving chromosome 8q and chromosome 20q when compared to the small lesions. Among pure high-grade tumors, small and large groups show specific genomic and phenotypic differences. Interestingly, larger tumors showed some molecular features associated with better prognosis. A more thorough evaluation of these differences could help identify the likelihood of recurrence or progression for in situ lesions. © 2011 Elsevier Inc.

Authors
Hwang, ES; Lal, A; Chen, Y-Y; Devries, S; Swain, R; Anderson, J; Roy, R; Waldman, FM
MLA Citation
Hwang, ES, Lal, A, Chen, Y-Y, Devries, S, Swain, R, Anderson, J, Roy, R, and Waldman, FM. "Genomic alterations and phenotype of large compared to small high-grade ductal carcinoma in situ." Human Pathology 42.10 (2011): 1467-1475.
PMID
21496874
Source
scival
Published In
Human Pathology
Volume
42
Issue
10
Publish Date
2011
Start Page
1467
End Page
1475
DOI
10.1016/j.humpath.2011.01.002

Characterizing the impact of 25 years of DCIS treatment

The significant increase in the detection and treatment of ductal carcinoma in situ (DCIS) since the introduction of screening mammography has not been accompanied by the anticipated reduction in invasive breast cancer (IBC) incidence. The prevalence of DCIS requires a reexamination of the population level effects of detecting and treating DCIS. To further our understanding of the possible impact of DCIS diagnosis and treatment on IBC incidence in the U.S., we simulated breast cancer incidence over 25 years under various assumptions regarding the baseline incidence of IBC and the progression of DCIS to IBC. The simulations demonstrate a tradeoff between the expected increased incidence of IBC absent any DCIS detection and treatment and the rate of progression of DCIS to IBC. Our analyses indicate that a high progression of DCIS to IBC implies a significant increase in incidence of IBC over what is observed had we not detected and treated DCIS. Conversely, if we assume that there would not have been a significant increase over and above the observed incidence evident in SEER, then our model indicates that the rate of DCIS progression to clinically significant IBC is low. Given the tradeoff illustrated by our model, we must reevaluate the assumption that DCIS is a short-term obligate precursor of invasive cancer and instead focus on further exploration of the true natural history of DCIS. © 2011 Springer Science+Business Media, LLC.

Authors
Ozanne, EM; Shieh, Y; Barnes, J; Bouzan, C; Hwang, ES; Esserman, LJ
MLA Citation
Ozanne, EM, Shieh, Y, Barnes, J, Bouzan, C, Hwang, ES, and Esserman, LJ. "Characterizing the impact of 25 years of DCIS treatment." Breast Cancer Research and Treatment 129.1 (2011): 165-173.
PMID
21390494
Source
scival
Published In
Breast Cancer Research and Treatment
Volume
129
Issue
1
Publish Date
2011
Start Page
165
End Page
173
DOI
10.1007/s10549-011-1430-5

The effect of system-level access factors on receipt of reconstruction among Latina and white women with DCIS

Treatment decisions associated with ductal carcinoma in situ (DCIS), including the decision to undergo breast reconstruction, may be more problematic for Latinas due to access and language issues. To help understand the factors that influence patients' receipt of reconstruction following mastectomy for DCIS, we conducted a population-based study of English- and Spanish-speaking Latina and non-Latina white women from 35 California counties. The objectives of this study were to identify the role of ethnicity and language in the receipt of reconstruction, the relationship between system-level factors and the receipt of reconstruction, and women's reasons for not undergoing reconstruction. Women aged 18 and older, who self-identified as Latina or non-Latino white and were diagnosed with DCIS between 2002 and 2005 were selected from eight California Cancer Registry (CCR) regions encompassing 35 counties. Approximately 24 months after diagnosis, they were surveyed about their DCIS treatment decisions. Survey data were merged with CCR records to obtain tumor and treatment data. The survey was successfully completed by 745 women, 239 of whom had a mastectomy and represent the sample included in this study. Whites had a higher completion rate than Latinas (67 and 55%, respectively). Analysis included descriptive statistics and logistic regression modeling. Mean age was 54 years. A greater proportion of whites had reconstruction (72%) compared to English-speaking Latinas (69%) and Spanish-speaking Latinas (40%). Multivariate analysis showed that women who were aged 65 and older, unemployed, and had a lower ratio of plastic surgeons in their county were less likely to have reconstructive surgery after mastectomy. The most frequent reasons mentioned not to receive reconstruction included lack of importance and desire to avoid additional surgery. Although ethnic/language differences in treatment selection were observed, multivariable analysis suggests that these differences could be explained by differential employment levels and geographic availability of plastic surgeons. © 2011 Springer Science+Business Media, LLC.

Authors
Kaplan, CP; Karliner, LS; Hwang, ES; Bloom, J; Stewart, S; Nickleach, D; Quinn, J; Thrasher, A; Nápoles, AM
MLA Citation
Kaplan, CP, Karliner, LS, Hwang, ES, Bloom, J, Stewart, S, Nickleach, D, Quinn, J, Thrasher, A, and Nápoles, AM. "The effect of system-level access factors on receipt of reconstruction among Latina and white women with DCIS." Breast Cancer Research and Treatment 129.3 (2011): 909-917.
PMID
21533531
Source
scival
Published In
Breast Cancer Research and Treatment
Volume
129
Issue
3
Publish Date
2011
Start Page
909
End Page
917
DOI
10.1007/s10549-011-1524-0

Language barriers and patient-centered breast cancer care

Objective: Provision of high quality patient-centered care is fundamental to eliminating healthcare disparities in breast cancer. We investigated physicians' experiences communicating with limited English proficient (LEP) breast cancer patients. Methods: Survey of a random sample of California oncologists and surgeons. Results: Of 301 respondents who reported treating LEP patients, 46% were oncologists, 75% male, 68% in private practice, and on average 33% of their patients had breast cancer. Only 40% reported at least sometimes using professional interpretation services. Although 75% felt they were usually able to communicate effectively with LEP patients, more than half reported difficulty discussing treatment options and prognosis, and 56% acknowledged having less-patient-centered treatment discussions with LEP breast cancer patients. In multivariate analysis, use of professional interpreters was associated with 53% lower odds of reporting less-patient-centered treatment discussions (OR 0.47; 95% CI 0.26-0.85). Conclusion: California surgeons and oncologists caring for breast cancer patients report substantial communication challenges when faced with a language barrier. Although use of professional interpreters is associated with more patient-centered communication, there is a low rate of professional interpreter utilization. Practice implications: Future research and policy should focus on increasing access to and reimbursement for professional interpreter services. © 2010 Elsevier Ireland Ltd.

Authors
Karliner, LS; Hwang, ES; Nickleach, D; Kaplan, CP
MLA Citation
Karliner, LS, Hwang, ES, Nickleach, D, and Kaplan, CP. "Language barriers and patient-centered breast cancer care." Patient Education and Counseling 84.2 (2011): 223-228.
PMID
20685068
Source
scival
Published In
Patient Education and Counseling
Volume
84
Issue
2
Publish Date
2011
Start Page
223
End Page
228
DOI
10.1016/j.pec.2010.07.009

Is radiation indicated in patients with ductal carcinoma in situ and close or positive mastectomy margins?

Purpose: Resection margin status is one of the most significant factors for local recurrence in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery with or without radiation. However, its impact on chest wall recurrence in patients treated with mastectomy is unknown. The purpose of this study was to determine chest wall recurrence rates in women with DCIS and close (<5 mm) or positive mastectomy margins in order to evaluate the potential role of radiation therapy. Methods and Materials: Between 1985 and 2005, 193 women underwent mastectomy for DCIS. Fifty-five patients had a close final margin, and 4 patients had a positive final margin. Axillary surgery was performed in 17 patients. Median follow-up was 8 years. Formal pathology review was conducted to measure and verify margin status. Nuclear grade, architectural pattern, and presence or absence of necrosis was recorded. Results: Median pathologic size of the DCIS in the mastectomy specimen was 4.5 cm. Twenty-two patients had DCIS of >5 cm or diffuse disease. Median width of the close final margin was 2 mm. Nineteen patients had margins of <1 mm. One of these 59 patients experienced a chest wall recurrence with regional adenopathy, followed by distant metastases 2 years following skin-sparing mastectomy. The DCIS was high-grade, 4 cm, with a 5-mm deep margin. A second patient developed an invasive cancer in the chest wall 20 years after her mastectomy for DCIS. This cancer was considered a new primary site arising in residual breast tissue. Conclusions: The risk of chest wall recurrence in this series of patients is 1.7% for all patients and 3.3% for high-grade DCIS. One out of 20 (5%) patients undergoing skin sparing or total skin-sparing mastectomy experienced a chest wall recurrence. This risk of a chest wall recurrence appears sufficiently low not to warrant a recommendation for postmastectomy radiation therapy for patients with margins of <5 mm. There were too few patients with positive margins to draw any firm conclusions. © 2011 Elsevier Inc.

Authors
Chan, LW; Rabban, J; Hwang, ES; Bevan, A; Alvarado, M; Ewing, C; Esserman, L; Fowble, B
MLA Citation
Chan, LW, Rabban, J, Hwang, ES, Bevan, A, Alvarado, M, Ewing, C, Esserman, L, and Fowble, B. "Is radiation indicated in patients with ductal carcinoma in situ and close or positive mastectomy margins?." International Journal of Radiation Oncology Biology Physics 80.1 (2011): 25-30.
PMID
20646871
Source
scival
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
80
Issue
1
Publish Date
2011
Start Page
25
End Page
30
DOI
10.1016/j.ijrobp.2010.01.044

Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy

Immune-regulated pathways influence multiple aspects of cancer development. In this article we demonstrate that both macrophage abundance and T-cell abundance in breast cancer represent prognostic indicators for recurrence-free and overall survival. We provide evidence that response to chemotherapy is in part regulated by these leukocytes; cytotoxic therapies induce mammary epithelial cells to produce monocyte/macrophage recruitment factors, including colony stimulating factor 1 (CSF1) and interleukin-34, which together enhance CSF1 receptor (CSF1R)-dependent macrophage infiltration. Blockade of macrophage recruitment with CSF1R-signaling antagonists, in combination with paclitaxel, improved survival of mammary tumor-bearing mice by slowing primary tumor development and reducing pulmonary metastasis. These improved aspects of mammary carcinogenesis were accompanied by decreased vessel density and appearance of antitumor immune programs fostering tumor suppression in a CD8 + T-cell-dependent manner. These data provide a rationale for targeting macrophage recruitment/ response pathways, notably CSF1R, in combination with cytotoxic therapy, and identification of a breast cancer population likely to benefit from this novel therapeutic approach. SIGNIFICANCE: These findings reveal that response to chemotherapy is in part regulated by the tumor immune microenvironment and that common cytotoxic drugs induce neoplastic cells to produce monocyte/macrophage recruitment factors, which in turn enhance macrophage infiltration into mammary adenocarcinomas. Blockade of pathways mediating macrophage recruitment, in combination with chemotherapy, significantly decreases primary tumor progression, reduces metastasis, and improves survival by CD8 + T-cell-dependent mechanisms, thus indicating that the immune microenvironment of tumors can be reprogrammed to instead foster antitumor immunity and improve response to cytotoxic therapy. © 2011 American Association for Cancer Research.

Authors
DeNardo, DG; Brennan, DJ; Rexhepaj, E; Ruffell, B; Shiao, SL; Madden, SF; Gallagher, WM; Wadhwani, N; Keil, SD; Junaid, SA; Rugo, HS; Hwang, ES; Jirström, K; West, BL; Coussens, LM
MLA Citation
DeNardo, DG, Brennan, DJ, Rexhepaj, E, Ruffell, B, Shiao, SL, Madden, SF, Gallagher, WM, Wadhwani, N, Keil, SD, Junaid, SA, Rugo, HS, Hwang, ES, Jirström, K, West, BL, and Coussens, LM. "Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy." Cancer Discovery 1.1 (2011): 54-67.
PMID
22039576
Source
scival
Published In
Cancer Discovery
Volume
1
Issue
1
Publish Date
2011
Start Page
54
End Page
67
DOI
10.1158/2159-8274.CD-10-0028

The impact of lobular histology on breast cancer treatment.

Lobular neoplasias are a distinct clinical entity with subtle differences in locoregional treatment considerations when compared with ductal cancers. Although overall surgical recommendations do not differ significantly between breast cancers of lobular versus ductal histology, there are important distinctions that should be considered as part of patient care, particularly with respect to recommendations regarding management of the contralateral breast and genetic testing. Because the lobular subtype of breast cancer is underrepresented in studies of molecular prognostic markers, the results of such testing must be interpreted with caution until they are validated specifically in patients with lobular histology. Until then, the mainstay of sound treatment decision-making remains a thorough clinical understanding of the disease and of the factors that can have an impact on outcome.

Authors
Hwang, ES
MLA Citation
Hwang, ES. "The impact of lobular histology on breast cancer treatment." Oncology (Williston Park, N.Y.) 25.4 (2011): 362-365.
PMID
21618959
Source
scival
Published In
Oncology
Volume
25
Issue
4
Publish Date
2011
Start Page
362
End Page
365

The impact of preoperative magnetic resonance imaging on surgical treatment and outcomes for ductal carcinoma in situ

Background: Although magnetic resonance imaging (MRI) is a useful imaging modality for invasive cancer, its role in preoperative surgical planning for ductal carcinoma in situ (DCIS) has not been established. We sought to determine whether preoperative MRI affects surgical treatment and outcomes in women with pure DCIS. Patients and Methods: We reviewed consecutive records of women diagnosed with pure DCIS on core biopsy between 2000 and 2007. Patient characteristics, surgical planning, and outcomes were compared between patients with and without preoperative MRI. Multivariable regression was performed to determine which covariates were independently associated with mastectomy or sentinel lymph node biopsy (SLNB). Results: Of 149 women diagnosed with DCIS, 38 underwent preoperative MRI. On univariate analysis, patients undergoing MRI were younger (50 years vs. 59 years; P < .001) and had larger DCIS size on final pathology (1.6 cm vs. 1.0 cm; P = .007) than those without MRI. Mastectomy and SLNB rates were significantly higher in the preoperative MRI group (45% vs. 14%, P < .001; and 47% vs. 23%, P = .004, respectively). However, there were no differences in number of re-excisions, margin status, and margin size between the two groups. On multivariate analysis, preoperative MRI and age were independently associated with mastectomy (OR, 3.16, P = .018; OR, 0.95, P = .031, respectively), while multifocality, size, and family history were not significant predictors. Conclusion: We found a strong association between preoperative MRI and mastectomy in women undergoing treatment for DCIS. Additional studies are needed to examine the increased rates of mastectomy as a possible consequence of preoperative MRI for DCIS.© 2011 Elsevier Inc. All rights reserved.

Authors
Itakura, K; Lessing, J; Sakata, T; Heinzerling, A; Vriens, E; Wisner, D; Alvarado, M; Esserman, L; Ewing, C; Hylton, N; Hwang, ES
MLA Citation
Itakura, K, Lessing, J, Sakata, T, Heinzerling, A, Vriens, E, Wisner, D, Alvarado, M, Esserman, L, Ewing, C, Hylton, N, and Hwang, ES. "The impact of preoperative magnetic resonance imaging on surgical treatment and outcomes for ductal carcinoma in situ." Clinical Breast Cancer 11.1 (2011): 33-38.
Source
scival
Published In
Clinical Breast Cancer
Volume
11
Issue
1
Publish Date
2011
Start Page
33
End Page
38
DOI
10.3816/CBC.2011.n.006

Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer patients

Background: Accurate intraoperative pathologic examination of sentinel lymph nodes (SLNs) has been an important tool that can reduce the need for reoperations in patients with SLN-positive breast cancer. The objective of the current study was to determine the accuracy of intraoperative frozen section (IFS) of SLNs during breast cancer surgery. Methods: The authors retrospectively reviewed the records of 326 patients with breast cancer who underwent IF analysis of SLNs at a single institution. Then, they conducted a meta-analysis that included 47 published studies of IFS of SLNs in patients with breast cancer. Results: Hematoxylin and eosin (H&E) staining revealed metastasis in SLNs in 99 patients (30.4%), including 61 patients with macrometastasis (MAM) (>2 mm) (the MAM group) and 38 patients with micrometastasis (Mi) or isolated tumor cell (ITC) deposits (the Mi/ITC group). The overall sensitivity of the institutional series was 60.6% (60 of 99 patients), and overall specificity was 100% (227 of 227 true negatives). The sensitivity of IFS was significantly lower in the Mi/ITC group (28.9%) than in the MAM group (80.3%; P <.0001). According to the meta-analysis of published studies and data from the author's institution (47 studies, for a total of 13,062 patients who underwent SLN dissection with IFS of SLNs), the mean sensitivity was 73%, and the mean specificity was 100%. The mean sensitivity was 94% for the MAM group and 40% for the Mi/ITC group. Conclusions: IFS of SLNs was more reliable for detecting MAM than for detecting Mi/ITC deposits. It lacked sufficient accuracy to rule out Mi/ITC deposits. © 2010 American Cancer Society.

Authors
Liu, L-C; Lang, JE; Lu, Y; Roe, D; Hwang, SE; Ewing, CA; Esserman, LJ; Morita, E; Treseler, P; Leong, SP
MLA Citation
Liu, L-C, Lang, JE, Lu, Y, Roe, D, Hwang, SE, Ewing, CA, Esserman, LJ, Morita, E, Treseler, P, and Leong, SP. "Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer patients." Cancer 117.2 (2011): 250-258.
PMID
20818649
Source
scival
Published In
Cancer
Volume
117
Issue
2
Publish Date
2011
Start Page
250
End Page
258
DOI
10.1002/cncr.25606

Selection of treatment among Latina and non-Latina white women with ductal carcinoma in situ

Background: The growing rates of ductal carcinoma in situ (DCIS) and evidence that Latinas may underuse breast-conserving surgery (BCS) compared with white women highlight the need to better understand how treatment decisions are made in this understudied group. To help address this gap, this study compared surgery and radiation treatment decision making among white and Spanish-speaking and English-speaking Latina women with DCIS recruited from eight population-based cancer registries from 35 California counties. Methods: Women aged ≥18 who self-identified as Latina or non-Latina white diagnosed with DCIS between 2002 and 2005 were selected from eight California Cancer Registry (CCR) regions and surveyed about their DCIS treatment decision making by telephone approximately 24 months after diagnosis. Survey data were merged with CCR hospital-based records to obtain tumor and treatment data. Results: Mean age was 57 years. Multivariate analysis indicated no differences by ethnicity or language in the receipt of mastectomy vs. BCS after controlling demographic, health, and personal preferences. English-speaking Latinas were more likely to receive radiation than their Spanish-speaking or white counterparts, controlling for demographic and other factors. Among women receiving BCS, physician recommendation was the strongest predictor of receipt of radiation. Conclusions: Ethnic disparities in surgical treatment choices after breast cancer diagnosis were not seen in this cohort of women diagnosed with DCIS. Physicians play an essential role in patients' treatment choices for DCIS, particularly for adjuvant radiation. © 2011, Mary Ann Liebert, Inc.

Authors
Kaplan, CP; Nápoles, AM; Hwang, ES; Bloom, J; Stewart, S; Nickleach, D; Karliner, L
MLA Citation
Kaplan, CP, Nápoles, AM, Hwang, ES, Bloom, J, Stewart, S, Nickleach, D, and Karliner, L. "Selection of treatment among Latina and non-Latina white women with ductal carcinoma in situ." Journal of Women's Health 20.2 (2011): 215-223.
PMID
21128819
Source
scival
Published In
Journal of Women's Health
Volume
20
Issue
2
Publish Date
2011
Start Page
215
End Page
223
DOI
10.1089/jwh.2010.1986

Impact of chemotherapy on postoperative complications after mastectomy and immediate breast reconstruction

Objectives: To determine the impact of chemotherapy and the timing of chemotherapy on postoperative outcomes after mastectomy and immediate breast reconstruction. Design: Retrospective review. Setting: University tertiary care institution. Patients: One hundred sixty-three consecutive patients undergoing mastectomy and immediate breast reconstruction. Intervention: Systemic chemotherapy for breast cancer. Main Outcome Measures: Postoperative complications following mastectomy and immediate breast reconstruction. Results: One hundred sixty-three patients underwent mastectomy and immediate breast reconstruction during the study period, with a mean postoperative follow-up of 19.2 months. Sixty-six percent of the patients had expander/implant reconstruction, while 33% underwent autologous reconstruction. Fifty-seven patients received neoadjuvant chemotherapy and 41 received postoperative chemotherapy. Eighteen patients (44%) in the adjuvant chemotherapy cohort developed postoperative infections, compared with 13 patients (23%) in the neoadjuvant chemotherapy group and 16 patients (25%) who did not receive any chemotherapy (P = .05). Overall, 31% of patients had a complication requiring an unplanned return to the operating room; this rate did not differ between groups (P = .79). Of patients who underwent expander/implant reconstruction, 8 women (26%) in the neoadjuvant chemotherapy cohort, 7 women (22%) in the adjuvant chemotherapy cohort, and 8 women (18%) without chemotherapy required expander or implant removal (P = .70). Conclusions: Although the highest rate of surgical site infections was in the adjuvant chemotherapy group, there were no differences between groups with respect to unplanned return to the operating room, expander loss, and donor-site complications. Neither the inclusion of chemotherapy nor the timing of its administration significantly affected the complication rates after mastectomy and immediate breast reconstruction in this population. ©2010 American Medical Association. All rights reserved.

Authors
Peled, AW; Itakura, K; Foster, RD; Hamolsky, D; Tanaka, J; Ewing, C; Alvarado, M; Esserman, LJ; Hwang, ES
MLA Citation
Peled, AW, Itakura, K, Foster, RD, Hamolsky, D, Tanaka, J, Ewing, C, Alvarado, M, Esserman, LJ, and Hwang, ES. "Impact of chemotherapy on postoperative complications after mastectomy and immediate breast reconstruction." Archives of Surgery 145.9 (2010): 880-885.
PMID
20855759
Source
scival
Published In
Archives of Surgery
Volume
145
Issue
9
Publish Date
2010
Start Page
880
End Page
885
DOI
10.1001/archsurg.2010.163

The impact of surgery on ductal carcinoma in situ outcomes: The use of mastectomy

Mastectomy has been the historical mainstay of treatment for ductal carcinoma in situ (DCIS), but over time, there have been significant changes in its use for preinvasive breast cancer. Although there was an early reduction in mastectomy rates for DCIS with the introduction of breast-conserving surgery, in some groups, the rates of both mastectomy and contralateral mastectomy for DCIS have increased in recent years. Due to advances in breast cancer screening as well as improvements in breast reconstruction, mastectomy will continue to be an important and acceptable treatment option. Recurrence is rare following mastectomy for DCIS. Nevertheless, there remains a need to follow patients for in-breast, nodal, or contralateral breast events, which can occur long after the index DCIS has been treated. Since up to 70% of women with newly diagnosed DCIS have disease that can be managed with breast-conserving surgery, patient counseling is imperative to ensure the best use of this option for DCIS, given that mastectomy does not significantly impact survival in this setting. © The Author 2010. Published by Oxford University Press. All rights reserved.

Authors
Hwang, ES
MLA Citation
Hwang, ES. "The impact of surgery on ductal carcinoma in situ outcomes: The use of mastectomy." Journal of the National Cancer Institute - Monographs 41 (2010): 197-199.
PMID
20956829
Source
scival
Published In
Journal of the National Cancer Institute. Monographs
Issue
41
Publish Date
2010
Start Page
197
End Page
199
DOI
10.1093/jncimonographs/lgq032

Status of intraductal therapy for ductal carcinoma in Situ

The intraductal approach is particularly appealing in the setting of ductal carcinoma in situ (DCIS), a preinvasive breast neoplasm that is thought to be entirely intraductal in its extent. Based on an emerging understanding of the anatomy of the ductal system as well as novel techniques to leverage the access accorded by the intraductal approach, researchers are actively exploring how ductal lavage, ductoscopy, and intraductal infusion of therapeutic agents may enhance breast cancer treatment. Both cytologic and molecular diagnostics continue to improve, and work is ongoing to identify the most effective diagnostic biomarkers for DCIS and cancer, although optimal targeting of the diseased duct remains an important consideration. Ductoscopy holds potential in detection of occult intraductal lesions, and ductoscopically guided lumpectomy could increase the likelihood of a more comprehensive surgical excision. Exciting pilot studies are in progress to determine the safety and feasibility of intraductal chemotherapy infusion. These studies are an important starting point for future investigations of intraductal ablative therapy for DCIS, because as our knowledge and techniques evolve, it is likely that DCIS may be the target most amenable to treatment by intraductal therapy. If such studies are successful, these approaches will allow an important and meaningful transformation in treatment options for women diagnosed with DCIS. © The Author(s) 2010.

Authors
Flanagan, M; Love, S; Hwang, ES
MLA Citation
Flanagan, M, Love, S, and Hwang, ES. "Status of intraductal therapy for ductal carcinoma in Situ." Current Breast Cancer Reports 2.2 (2010): 75-82.
Source
scival
Published In
Current Breast Cancer Reports
Volume
2
Issue
2
Publish Date
2010
Start Page
75
End Page
82
DOI
10.1007/s12609-010-0015-3

Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer

The purpose of this study is to determine the biologic impact of short-term lipophilic statin exposure on in situ and invasive breast cancer through paired tissue, blood and imaging-based biomarkers. A perioperative window trial of fluvastatin was conducted in women with a diagnosis of DCIS or stage 1 breast cancer. Patients were randomized to high dose (80 mg/day) or low dose (20 mg/day) fluvastatin for 3-6 weeks before surgery. Tissue (diagnostic core biopsy/final surgical specimen), blood, and magnetic resonance images were obtained before/after treatment. The primary endpoint was Ki-67 (proliferation) reduction. Secondary endpoints were change in cleaved caspase-3 (CC3, apoptosis), MRI tumor volume, and serum C-reactive protein (CRP, inflammation). Planned subgroup analyses compared disease grade, statin dose, and estrogen-receptor status. Forty of 45 patients who enrolled completed the protocol; 29 had paired Ki-67 primary endpoint data. Proliferation of high grade tumors decreased by a median of 7.2% (P = 0.008), which was statistically greater than the 0.3% decrease for low grade tumors. Paired data for CC3 showed tumor apoptosis increased in 38%, remained stable in 41%, and decreased in 21% of subjects. More high grade tumors had an increase in apoptosis (60 vs. 13%; P = 0.015). Serum CRP did not change, but cholesterol levels were significantly lower post statin exposure (P < 0.001). Fluvastatin showed measurable biologic changes by reducing tumor proliferation and increasing apoptotic activity in high-grade, stage 0/1 breast cancer. Effects were only evident in high grade tumors. These results support further evaluation of statins as chemoprevention for ER-negative high grade breast cancers. © 2009 Springer Science+Business Media, LLC.

Authors
Garwood, ER; Kumar, AS; Baehner, FL; Moore, DH; Au, A; Hylton, N; Flowers, CI; Garber, J; Lesnikoski, B-A; Hwang, ES; Olopade, O; Port, ER; Campbell, M; Esserman, LJ
MLA Citation
Garwood, ER, Kumar, AS, Baehner, FL, Moore, DH, Au, A, Hylton, N, Flowers, CI, Garber, J, Lesnikoski, B-A, Hwang, ES, Olopade, O, Port, ER, Campbell, M, and Esserman, LJ. "Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer." Breast Cancer Research and Treatment 119.1 (2010): 137-144.
PMID
19728082
Source
scival
Published In
Breast Cancer Research and Treatment
Volume
119
Issue
1
Publish Date
2010
Start Page
137
End Page
144
DOI
10.1007/s10549-009-0507-x

Genetic and phenotypic characteristics of pleomorphic lobular carcinoma in situ of the breast

The clinical, pathologic, and molecular features of pleomorphic lobular carcinoma in situ (PLCIS) and the relationship of PLCIS to classic LCIS (CLCIS) are poorly defined. In this study, we analyzed 31 cases of PLCIS (13 apocrine and 18 nonapocrine subtypes) and compared the clinical, pathologic, immunophenotypic, and genetic characteristics of these cases with those of 24 cases of CLCIS. Biomarker expression was examined using immunostaining for E-cadherin, gross cystic disease fluid protein-15, estrogen, progesterone, androgen receptor, human epidermal growth factor receptor2, CK5/6, and Ki67. Array-based comparative genomic hybridization to assess the genomic alterations was performed using microdissected formalin-fixed paraffin-embedded samples. Patients with PLCIS presented with mammographic abnormalities. Histologically, the tumor cells were dyshesive and showed pleomorphic nuclei, and there was often associated necrosis and microcalcifications. All lesions were E-cadherin negative. Compared with CLCIS, PLCIS showed significantly higher Ki67 index, lower estrogen receptor and progesterone receptor expression, and higher incidence of HER2 gene amplification. The majority of PLCIS and CLCIS demonstrated loss of 16q and gain of 1q. Apocrine PLCIS had significantly more genomic alterations than CLCIS and nonapocrine PLCIS. Although lack of E-cadherin expression and the 16q loss and 1q gain-array-based comparative genomic hybridization pattern support a relationship to CLCIS, PLCIS has clinical, mammographic, histologic, immunophenotypic, and genetic features that distinguish it from CLCIS. The histologic features, biomarker profile, and genomic instability observed in PLCIS suggest a more aggressive phenotype than CLCIS. However, clinical follow-up studies will be required to define the natural history and most appropriate management of these lesions. Copyright © 2009 by Lippincott Williams & Wilkins.

Authors
Chen, Y-Y; Hwang, E-SS; Roy, R; Devries, S; Anderson, J; Wa, C; Fitzgibbons, PL; Jacobs, TW; MacGrogan, G; Peterse, H; Vincent-Salomon, A; Tokuyasu, T; Schnitt, SJ; Waldman, FM
MLA Citation
Chen, Y-Y, Hwang, E-SS, Roy, R, Devries, S, Anderson, J, Wa, C, Fitzgibbons, PL, Jacobs, TW, MacGrogan, G, Peterse, H, Vincent-Salomon, A, Tokuyasu, T, Schnitt, SJ, and Waldman, FM. "Genetic and phenotypic characteristics of pleomorphic lobular carcinoma in situ of the breast." American Journal of Surgical Pathology 33.11 (2009): 1683-1694.
PMID
19701073
Source
scival
Published In
American Journal of Surgical Pathology
Volume
33
Issue
11
Publish Date
2009
Start Page
1683
End Page
1694
DOI
10.1097/PAS.0b013e3181b18a89

Bacteriologic features of surgical site infections following breast surgery

Background: Perioperative antibiotic prophylaxis to prevent surgical site infections (SSIs) after breast surgery is common practice. Breast SSIs were investigated to determine bacterial isolates, resistance patterns, and the appropriateness of cefazolin, the authors' institution's current regimen for perioperative antibiotic prophylaxis. Methods: A retrospective review of 53 patients with culture-positive breast SSIs between June 1997 and August 2008 identified patient characteristics, bacterial isolates, and microbial resistance patterns. Results: Among the 53 patients with positive cultures, 42% (n = 22) had undergone mastectomy, and 34% (n = 18) had undergone lumpectomy. Sixty-three bacterial isolates were identified, with 15% of SSIs being polymicrobial. Of the isolates, 49% (n = 31) were gram-negative bacteria. There was only 1 case of methicillin-resistant Staphylococcus aureus. Eight of 63 (13%) gram-negative isolates were cefazolin resistant. Conclusions: Gram-negative SSIs constituted half of the SSIs in this breast surgery cohort. Of all breast isolates, 17.5% were resistant to cefazolin. On the basis of these findings, antibiotic prophylaxis regimens alternative to cefazolin should be considered. © 2009 Elsevier Inc. All rights reserved.

Authors
Mukhtar, RA; Throckmorton, AD; Alvarado, MD; Ewing, CA; Esserman, LJ; Chiu, C; Hwang, ES
MLA Citation
Mukhtar, RA, Throckmorton, AD, Alvarado, MD, Ewing, CA, Esserman, LJ, Chiu, C, and Hwang, ES. "Bacteriologic features of surgical site infections following breast surgery." American Journal of Surgery 198.4 (2009): 529-531.
PMID
19800462
Source
scival
Published In
The American Journal of Surgery
Volume
198
Issue
4
Publish Date
2009
Start Page
529
End Page
531
DOI
10.1016/j.amjsurg.2009.06.006

Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ

Background: Endocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS). However, it is unknown whether a neoadjuvant (preoperative) anti-estrogen approach to DCIS results in any biological change. This study was undertaken to investigate the pathologic and biomarker changes in DCIS following neoadjuvant endocrine therapy compared to a group of patients who did not undergo preoperative anti-estrogenic treatment to determine whether such treatment results in detectable histologic alterations. Methods: Patients (n = 23) diagnosed with ER-positive pure DCIS by stereotactic core biopsy were enrolled in a trial of neoadjuvant anti-estrogen therapy followed by definitive excision. Patients on hormone replacement therapy, with palpable masses, or with histologic or clinical suspicion of invasion were excluded. Premenopausal women were treated with tamoxifen and postmenopausal women were treated with letrozole. Pathologic markers of proliferation, inflammation, and apoptosis were evaluated at baseline and at three months. Results: Biomarker changes were compared to a cohort of patients who had not received preoperative treatment. Conclusion: Median age of the cohort was 53 years (range 38-78); 14 were premenopausal. Following treatment, predominant morphologic changes included increased multinucleated histiocytes and degenerated cells, decreased duct extension, and prominent periductal fibrosis. Two postmenopausal patients had ADH only with no residual DCIS at excision. Postmenopausal women on letrozole had significant reduction of PR, and Ki67 as well as increase in CD68-positive cells. For premenopausal women on tamoxifen treatment, the only significant change was increase in CD68. No change in cleaved caspase 3 was found. Two patients had invasive cancer at surgery. Trial Registration: Preoperative therapy for DCIS is associated with significant pathologic alterations. These changes may be clinically significant. Further work is needed to identify which women may be the best candidates for such treatment for DCIS, and whether best responders may safely avoid surgical intervention. ClinicalTrials.gov NCT00290745. © 2009 Chen et al; licensee BioMed Central Ltd.

Authors
Chen, Y-Y; DeVries, S; Anderson, J; Lessing, J; Swain, R; Chin, K; Shim, V; Esserman, LJ; Waldman, FM; Hwang, ES
MLA Citation
Chen, Y-Y, DeVries, S, Anderson, J, Lessing, J, Swain, R, Chin, K, Shim, V, Esserman, LJ, Waldman, FM, and Hwang, ES. "Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ." BMC Cancer 9 (2009): 285--.
PMID
19689789
Source
scival
Published In
BMC Cancer
Volume
9
Publish Date
2009
Start Page
285-
DOI
10.1186/1471-2407-9-285

Total skin-sparing mastectomy: Complications and local recurrence rates in 2 cohorts of patients

Purpose: Dissemination of the total skin-sparing mastectomy (TSSM) technique is limited by concerns of nipple viability, flap necrosis, local recurrence risk, and the technical challenge of this procedure. We sought to define the impact of surgical and reconstructive variables on complication rates and assess how changes in technique affect outcomes. PATIENTS AND Methods: We compared the outcomes of TSSM in 2 cohorts of patients. Cohort 1: the first 64 TSSM procedures performed at our institution, between 2001 and 2005. Cohort 2: 106 TSSM performed between 2005 and 2007. Outcomes of cohort 1 were analyzed in 2005. At that time, potential risk factors for complications were identified, and efforts to minimize these risks by altering operative and reconstructive technique were then applied to patients in cohort 2. The impact of these changes on outcomes was assessed. Logistic regression was used to determine the association between predictor variables and adverse outcomes (Stata 10). Results: The predominant incision type in cohort 2 involved less than a third of the nipple areola complex (NAC), and the most frequent reconstruction technique was tissue expander placement. Between cohort 1 and cohort 2, nipple survival rates rose from 80% to 95% (P = 0.003) and complication rates declined: necrotic complications (30% → 13%; P = 0.01), implant loss (31% → 10%; P = 0.005), skin flap necrosis (16%-11%; not significant), and significant infections (17%-9%, not significant). Incisions involving >30% of the NAC (P < 0.001) and reconstruction with autologous tissue (P < 0.001) were independent risk factors for necrotic complications. The local recurrence rate was 0.6% at a median follow-up of 13 months (range, 1-65), with no recurrences in the NAC. Conclusion: Focused improvement in technique has resulted in the development of TSSM as a successful intervention at our institution that is oncologically safe with high nipple viability and early low rates of recurrence. Identifying factors that contribute to complications and changing surgical and reconstructive techniques to eliminate risk factors has greatly improved outcomes. © 2009 by Lippincott Williams & Wilkins.

Authors
Garwood, ER; Moore, D; Ewing, C; Hwang, ES; Alvarado, M; Foster, RD; Esserman, LJ
MLA Citation
Garwood, ER, Moore, D, Ewing, C, Hwang, ES, Alvarado, M, Foster, RD, and Esserman, LJ. "Total skin-sparing mastectomy: Complications and local recurrence rates in 2 cohorts of patients." Annals of Surgery 249.1 (2009): 26-32.
PMID
19106672
Source
scival
Published In
Annals of Surgery
Volume
249
Issue
1
Publish Date
2009
Start Page
26
End Page
32
DOI
10.1097/SLA.0b013e31818e41a7

Protein acetylation and histone deacetylase expression associated with malignant breast cancer progression

Purpose: Excess histone deacetylase (HDAC) activity can induce hypoacetylation of histone and nonhistone protein substrates, altering gene expression patterns and cell behavior potentially associated with malignant transformation. However, HDAC expression and protein acetylation have not been studied in the context of breast cancer progression. Experimental Design: We assessed expression levels of acetylated histone H4 (ac-H4), ac-H4K12, ac-tubulin, HDAC1, HDAC2, and HDAC6 in 22 reduction mammoplasties and in 58 specimens with synchronous normal epithelium, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) components. Differences among groups were tested for significance using nonparametric tests. Results: From normal epithelium to DCIS, there was a marked reduction in histone acetylation (P < 0.0001). Most cases showed similar levels of acetylation in DCIS and IDC, although some showed further reduction of ac-H4 and ac-H4K12 from DCIS to IDC. Expression of HDAC1, HDAC2, and HDAC6 was also significantly reduced but by a smaller magnitude. Greater reductions of H4 acetylation and HDAC1 levels were observed from normal to DCIS in estrogen receptor-negative compared with estrogen receptor-positive, and in high-grade compared with non-high-grade tumors. Conclusion: Overall, there was a global pattern of hypoacetylation associated with progression from normal to DCIS to IDC. These findings suggest that the reversal of this hypoacetylation in DCIS and IDC could be an early measure of HDAC inhibitor activity. ©2009 American Association for Cancer Research.

Authors
Suzuki, J; Chen, Y-Y; Scott, GK; DeVries, S; Chin, K; Benz, CC; Waldman, FM; Hwang, ES
MLA Citation
Suzuki, J, Chen, Y-Y, Scott, GK, DeVries, S, Chin, K, Benz, CC, Waldman, FM, and Hwang, ES. "Protein acetylation and histone deacetylase expression associated with malignant breast cancer progression." Clinical Cancer Research 15.9 (2009): 3163-3171.
PMID
19383825
Source
scival
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
15
Issue
9
Publish Date
2009
Start Page
3163
End Page
3171
DOI
10.1158/1078-0432.CCR-08-2319

Prognostic implications of positive nonsentinel lymph nodes removed during selective sentinel lymphadenectomy for breast cancer

Nonsentinel lymph nodes (SLNs) are commonly removed at the time of selective sentinel lymphadenectomy (SSL). Their predictive value for the rest of the nodal basin is unknown. A retrospective review of 436 breast cancer patients who underwent SSL between 12/97 and 04/03 at a single institution. One-hundred nineteen patients had non-SLNs removed at SSL; eight were positive (6.7%). Positive non-SLNs predicted that SLNs would also be positive (p = 0.008). There was no difference in rates of additional positive nodes found on completion axillary node dissection between the non-SLN and SLN positive patients (p = 0.62). After adjustment for covariates, the presence of positive non-SLNs was not associated with poorer disease free survival (p = 0.24), time to systemic recurrence (p = 0.57), or overall survival (p = 0.70). Positive non-SLNs removed during SSL are not a significant risk factor for additional positive nodes on completion axillary nodal dissection (CALND) or for worse survival than positive SLNs. © 2009 Wiley Periodicals, Inc.

Authors
Lang, JE; Liu, L-C; Lu, Y; Jenkins, T; Hwang, SE; Esserman, LJ; Ewing, CA; Alvarado, M; Morita, E; Treseler, P; Leong, SP
MLA Citation
Lang, JE, Liu, L-C, Lu, Y, Jenkins, T, Hwang, SE, Esserman, LJ, Ewing, CA, Alvarado, M, Morita, E, Treseler, P, and Leong, SP. "Prognostic implications of positive nonsentinel lymph nodes removed during selective sentinel lymphadenectomy for breast cancer." Breast Journal 15.3 (2009): 242-246.
PMID
19645778
Source
scival
Published In
The Breast Journal
Volume
15
Issue
3
Publish Date
2009
Start Page
242
End Page
246
DOI
10.1111/j.1524-4741.2009.00712.x

Is It Necessary to Harvest Additional Lymph Nodes after Resection of the Most Radioactive Sentinel Lymph Node in Breast Cancer?

Background: No consensus exists about the number of sentinel lymph nodes (SLNs) that should be removed based on radioactivity counts in breast cancer, although the "10% rule" is often used. We hypothesized that the node with the highest radioactivity would have the strongest probability of being a positive SLN, and we sought to determine the lowest radioactive count of a node harboring cancer. Study Design: We retrospectively studied 332 breast cancer patients who underwent lymphoscintigraphy by injection of technetium 99m-labeled thiosulfate colloid and sentinel lymphadenectomy (SL) between 1997 and 2006, with intraoperative determination of radioactive counts of nodes by a gamma probe. All SLNs were examined by permanent sections consisting of at least 3 levels of 40- to 100-μm intervals for hematoxylin and eosin evaluation, with or without immunohistochemical staining for cytokeratins. Results: Seventy-four percent of patients had more than 1 SLN removed (mean 2.8 per patient); 23.5% had SLN metastasis. Of the node-positive patients, the hottest SLN was positive in 85.9% (67 of 78). Five of the 78 patients (6.4%) with positive nodes had counts less than 10% of those of the hottest node. The lowest radioactive count of a positive SLN was 4.2% of that of the hottest node. Lymphatic mapping based on the 10% rule could greatly improve the false-negative rates compared with removing only the hottest SLN (14.1% versus 6.4%). Conclusions: Most positive SLNs had the highest radioactivity. Our institutional experience indicates that to obtain an acceptable false-negative rate, nodes should be removed until the 10% rule is met. © 2008 American College of Surgeons.

Authors
Liu, L-C; Lang, JE; Jenkins, T; Lu, Y; Ewing, CA; Hwang, SE; Sokol, S; Alvarado, M; Esserman, LJ; Morita, E; Treseler, P; Leong, SP
MLA Citation
Liu, L-C, Lang, JE, Jenkins, T, Lu, Y, Ewing, CA, Hwang, SE, Sokol, S, Alvarado, M, Esserman, LJ, Morita, E, Treseler, P, and Leong, SP. "Is It Necessary to Harvest Additional Lymph Nodes after Resection of the Most Radioactive Sentinel Lymph Node in Breast Cancer?." Journal of the American College of Surgeons 207.6 (2008): 853-858.
PMID
19183531
Source
scival
Published In
Journal of The American College of Surgeons
Volume
207
Issue
6
Publish Date
2008
Start Page
853
End Page
858
DOI
10.1016/j.jamcollsurg.2008.08.008

Type and Duration of Exogenous Hormone Use Affects Breast Cancer Histology

Authors
Hwang, ES
MLA Citation
Hwang, ES. "Type and Duration of Exogenous Hormone Use Affects Breast Cancer Histology." 2008. 23-25.
Source
scival
Volume
19
Publish Date
2008
Start Page
23
End Page
25
DOI
10.1016/S1043-321X(08)80004-5

1–5 Multiple primary tumours in women following breast cancer, 1973–2000

Authors
Hwang, ES
MLA Citation
Hwang, ES. "1–5 Multiple primary tumours in women following breast cancer, 1973–2000." April 2007. 29-30.
Source
crossref
Volume
18
Publish Date
2007
Start Page
29
End Page
30
DOI
10.1016/S1043-321X(07)80010-5

Surgery for palliation and treatment of advanced breast cancer

The palliative benefits of surgery in patients with stage IV breast cancer have long been appreciated. Optimizing patient comfort and quality of life are critically important goals in these patients, most of whom have limited life expectancy. Advancements in reconstructive techniques have allowed for closure of extensive and complex defects of the chest wall and surrounding soft tissue without the need to sacrifice oncologic goals. However, care must be taken to weigh the extent of surgery and reconstruction against the possible delay to radiation and systemic treatment, as multimodality therapy offers the best chance for durable symptom management in these challenging patients. The emergence of increasingly effective systemic therapies has also created the need to address resectable primary sites as well as distant sites in women with metastatic breast cancer, as many can expect to survive for many years with stable disease. Several models of cancer and metastatic progression have been proposed. However, the significant challenge of identifying those patients who may most gain from local surgery remains. This question is ideally suited for multi-institutional prospective, randomized controlled trials, as no single institution alone has sufficient experience to definitively address these issues. Careful consideration must be given to incorporating disease extent, sites of involvement, patient comorbidities and rate of progression into the study design. Furthermore, genomic and proteomic phenotyping of tumors may in future prove to be important criteria for patient selection for "targeted" surgical therapy and must be a fundamental component of these studies. The new generation of prospective clinical trials of surgery for stage IV breast cancer patients may identify a subset of women who may benefit from incorporating surgery into a multimodality treatment plan, leading to improved quality of life, survival and potential cure in women with advanced disease. © 2007.

Authors
Alvarado, M; Ewing, CA; Elyassnia, D; Foster, RD; Hwang, ES
MLA Citation
Alvarado, M, Ewing, CA, Elyassnia, D, Foster, RD, and Hwang, ES. "Surgery for palliation and treatment of advanced breast cancer." Surgical Oncology 16.4 (2007): 249-257.
PMID
17976977
Source
scival
Published In
Surgical Oncology
Volume
16
Issue
4
Publish Date
2007
Start Page
249
End Page
257
DOI
10.1016/j.suronc.2007.08.007

Association between breast density and subsequent breast cancer following treatment for ductal carcinoma in situ

Background: Risk of invasive cancer following treatment for ductal carcinoma in situ (DCIS) is associated with both treatment- and tumor-related factors. However, it is unknown whether stromal factors such as breast density may also influence subsequent invasive breast events. We investigated whether breast density is an independent predictor of subsequent breast events among women treated for DCIS. Population: A prospective cohort study of 3,274 women ages 30 to 93 in the Breast Cancer Surveillance Consortium treated with lumpectomy for DCIS between 1993 and 2005. All subjects had an American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density measure recorded prior to diagnosis. Methods: Ipsilateral and contralateral breast cancer following lumpectomy for DCIS were ascertained through state tumor registries, regional Surveillance Epidemiology and End Results program or pathology databases. A Cox proportional hazard model was used to compare adjusted risk of breast cancer among women with high (BI-RADS 3 or 4) versus low (BIRADS 1 or 2) breast density. Results: During a median follow-up period of 39 months (0-132 months), 133 women developed invasive breast cancer. After adjusting for age and radiation treatment, high breast density was associated with increased hazard for contralateral (hazard ratio, 3.1; 95% confidence interval, 1.6-6.1) but not ipsilateral (hazard ratio, 1.0; 95% confidence interval, 0.6-1.6) invasive breast events. Conclusion: High breast density is associated with contralateral, but not ipsilateral, invasive breast cancer following lumpectomy for DCIS. Thus, women with DCIS and high breast density may especially benefit from antiestrogenic therapy to reduce the risk of contralateral invasive disease. Copyright © 2007 American Association for Cancer Research.

Authors
Hwang, ES; Miglioretti, DL; Ballard-Barbash, R; Weaver, DL; Kerlikowske, K
MLA Citation
Hwang, ES, Miglioretti, DL, Ballard-Barbash, R, Weaver, DL, and Kerlikowske, K. "Association between breast density and subsequent breast cancer following treatment for ductal carcinoma in situ." Cancer Epidemiology Biomarkers and Prevention 16.12 (2007): 2587-2593.
PMID
18086762
Source
scival
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
16
Issue
12
Publish Date
2007
Start Page
2587
End Page
2593
DOI
10.1158/1055-9965.EPI-07-0458

Response [5]

Authors
Ozanne, EM; Hwang, ES; Esserman, LJ
MLA Citation
Ozanne, EM, Hwang, ES, and Esserman, LJ. "Response [5]." Breast Journal 13.5 (2007): 540-542.
Source
scival
Published In
The Breast Journal
Volume
13
Issue
5
Publish Date
2007
Start Page
540
End Page
542
DOI
10.1111/j.1524-4741.2007.00487.x

Information exchange and decision making in the treatment of Latina and White women with ductal carcinoma in situ

The natural history of ductal carcinoma in situ (DCIS) is largely unknown, and its optimal treatment remains controversial. Using semi-structured interviews, this study compared 18 White and 16 Latina women's understanding of their DCIS diagnosis, treatment decision-making processes, and satisfaction with care. Ethnic differences were observed in cognitive and emotional responses to DCIS, with White women generally reporting a better understanding of their diagnosis and treatment, and Latinas reporting more distress. Regardless of ethnicity, women with DCIS preferred that physicians discuss treatment options and attend to their informational and emotional needs. Satisfaction was associated with adequate information, expediency of care, and physicians' sensitivity to patients' emotional needs. Copyright © by The Haworth Press, Inc. All rights reserved.

Authors
Nápoles-Springer, AM; Livaudais, JC; Bloom, J; Hwang, S; Kaplan, CP
MLA Citation
Nápoles-Springer, AM, Livaudais, JC, Bloom, J, Hwang, S, and Kaplan, CP. "Information exchange and decision making in the treatment of Latina and White women with ductal carcinoma in situ." Journal of Psychosocial Oncology 25.4 (2007): 19-36.
PMID
18032263
Source
scival
Published In
Journal of Psychosocial Oncology
Volume
25
Issue
4
Publish Date
2007
Start Page
19
End Page
36
DOI
10.1300/J077v25n04_02

Identification of a robust gene signature that predicts breast cancer outcome in independent data sets

Background: Breast cancer is a heterogeneous disease, presenting with a wide range of histologic, clinical, and genetic features. Microarray technology has shown promise in predicting outcome in these patients. Methods: We profiled 162 breast tumors using expression microarrays to stratify tumors based on gene expression. A subset of 55 tumors with extensive follow-up was used to identify gene sets that predicted outcome. The predictive gene set was further tested in previously published data sets. Results: We used different statistical methods to identify three gene sets associated with disease free survival. A fourth gene set, consisting of 21 genes in common to all three sets, also had the ability to predict patient outcome. To validate the predictive utility of this derived gene set, it was tested in two published data sets from other groups. This gene set resulted in significant separation of patients on the basis of survival in these data sets, correctly predicting outcome in 62-65% of patients. By comparing outcome prediction within subgroups based on ER status, grade, and nodal status, we found that our gene set was most effective in predicting outcome in ER positive and node negative tumors. Conclusion: This robust gene selection with extensive validation has identified a predictive gene set that may have clinical utility for outcome prediction in breast cancer patients. © 2007 Korkola et al; licensee BioMed Central Ltd.

Authors
Korkola, JE; Blaveri, E; DeVries, S; II, DHM; Hwang, ES; Chen, Y-Y; Estep, ALH; Chew, KL; Jensen, RH; Waldman, FM
MLA Citation
Korkola, JE, Blaveri, E, DeVries, S, II, DHM, Hwang, ES, Chen, Y-Y, Estep, ALH, Chew, KL, Jensen, RH, and Waldman, FM. "Identification of a robust gene signature that predicts breast cancer outcome in independent data sets." BMC Cancer 7 (2007).
PMID
17428335
Source
scival
Published In
BMC Cancer
Volume
7
Publish Date
2007
DOI
10.1186/1471-2407-7-61

Ductal carcinoma in situ in BRCA mutation carriers

Purpose: The current literature suggests that ductal carcinoma in situ (DCIS) of the breast is infrequently diagnosed in patients with BRCA germline mutations. We studied women at high risk of hereditary breast cancer syndromes who underwent testing for BRCA1 and BRCA2 to estimate DCIS prevalence and incidence in known BRCA-positive women compared with high-risk women who were mutation negative. Methods: We analyzed breast event outcomes in a retrospective cohort of 129 BRCA-positive and 269 BRCA-negative women undergoing genetic testing for a BRCA mutation between September 1996 and December 2003 at University of California, San Francisco. We estimated the frequency of DCIS and invasive cancer and time to breast events from birth using a Cox proportional hazard model for competing risks. Histologic grade of DCIS was also compared between groups. Results: Among BRCA carriers, 48 (37%) had DCIS (with or without invasive cancer) compared with 92 noncarriers (34%). Univariate analysis showed that both DCIS and invasive cancer had an earlier onset in mutation carriers than in noncarriers, although on a per-woman basis, this difference was not statistically significant. High-grade DCIS was more common in BRCA1 mutation carriers than in patients without a mutation (P = .02). Conclusion: DCIS is equally as prevalent in patients who carry deleterious BRCA mutations as in high familial-risk women who are noncarriers, but occurs at an earlier age. Our results argue for the consideration of DCIS as a criterion for BRCA risk assessments with appropriate weighting in prediction models such as BRCAPRO. © 2007 by American Society of Clinical Oncology.

Authors
Hwang, ES; McLennan, JL; Moore, DH; Crawford, BB; Esserman, LJ; Ziegler, JL
MLA Citation
Hwang, ES, McLennan, JL, Moore, DH, Crawford, BB, Esserman, LJ, and Ziegler, JL. "Ductal carcinoma in situ in BRCA mutation carriers." Journal of Clinical Oncology 25.6 (2007): 642-647.
PMID
17210933
Source
scival
Published In
Journal of Clinical Oncology
Volume
25
Issue
6
Publish Date
2007
Start Page
642
End Page
647
DOI
10.1200/JCO.2005.04.0345

Type and duration of exogenous hormone use affects breast cancer histology

Background: It is unclear whether hormone replacement therapy (HRT), in addition to increasing risk for breast cancer, affects the type of breast cancer diagnosed. We conducted this investigation to assess whether the type of hormone used (none, estrogen, progesterone, or combined) and duration of use influences subsequent breast cancer histology. Methods: We performed a retrospective cohort analysis among women listed as incident cases of breast malignancy in the Kaiser Permanente Northern California Cancer Registry during 2003 (n = 2830). Type and duration of hormone used (none, estrogen, progesterone, or combined) before breast cancer diagnosis was obtained from electronic pharmacy records. The association between type and duration of hormone use with characteristics of subsequent breast cancers was examined. Results: Among women aged >50 years (n = 1701), any use of estrogen, progesterone, or combination therapy was not associated with an increased risk of estrogen receptor (ER)-positive disease. However, >6 months' use of combined HRT increased the odds of ER-positive tumors (odds ratio, 1.65; 95% confidence interval, 1.07-2.5; P = .02). Estrogen HRT patients were more likely than nonusers to present with low-grade (P = .05), and early-stage tumors (P = .03). This trend was not seen in combined HRT users. Conclusions: Short-duration HRT did not increase the likelihood of ER-positive breast cancer. However, prolonged duration of combined HRT, but not estrogen or progesterone alone, resulted in a marked increase in ER-positive disease. Our findings suggest that the effect of combined HRT on breast cancer incidence or progression is not immediate and that long-term use is more likely to affect breast cancer histology. © 2006 Society of Surgical Oncology.

Authors
Kumar, AS; Cureton, E; Shim, V; Sakata, T; Moore, DH; Benz, CC; Esserman, LJ; Hwang, ES
MLA Citation
Kumar, AS, Cureton, E, Shim, V, Sakata, T, Moore, DH, Benz, CC, Esserman, LJ, and Hwang, ES. "Type and duration of exogenous hormone use affects breast cancer histology." Annals of Surgical Oncology 14.2 (2007): 695-703.
PMID
17103262
Source
scival
Published In
Annals of Surgical Oncology
Volume
14
Issue
2
Publish Date
2007
Start Page
695
End Page
703
DOI
10.1245/s10434-006-9129-2

Total Skin-Sparing Mastectomy Without Preservation of the Nipple-Areola Complex

Authors
Hwang, ES; Esserman, LJ
MLA Citation
Hwang, ES, and Esserman, LJ. "Total Skin-Sparing Mastectomy Without Preservation of the Nipple-Areola Complex." October 2006. 251-252.
Source
crossref
Volume
17
Publish Date
2006
Start Page
251
End Page
252
DOI
10.1016/S1043-321X(06)80511-4

Magnetic resonance imaging captures the biology of ductal carcinoma in situ

Purpose: Magnetic resonance imaging (MRI) is an important tool for characterizing invasive breast cancer but has proven to be more challenging in the setting of ductal carcinoma in situ (DCIS). We investigated whether MRI features of DCIS reflect differences in biology and pathology. Patients and Methods: Forty five of 100 patients with biopsy-proven DCIS who underwent MRI and had sufficient tissue to be characterized by pathologic (nuclear grade, presence of comedo necrosis, size, and density of disease) and immunohistochemical (IHC) findings (proliferation, Ki67; angiogenesis, CD34; and inflammation, CD68). Pathology and MRI features (enhancement patterns, distribution, size, and density) were analyzed using pairwise and canonical correlations. Results: Histopathologic and IHC variables correlated with MRI features (r = 0.73). The correlation was largely due to size, density (by either MRI or pathology), and inflammation (P < .05). Most small focal masses were estrogen receptor-positive. MRI enhancement patterns that were clumped were more likely than heterogeneous patterns to be high-grade lesions. Homogenous lesions were large, high grade, and rich in macrophages. Presence of comedo necrosis and size could be distinguished on MRI (P < .05). MRI was most likely to over-represent the size of less dense, diffuse DCIS lesions. Conclusion: The heterogeneous presentation of DCIS on MRI reflects underlying histopathologic differences. © 2006 by American Society of Clinical Oncology.

Authors
Esserman, LJ; Kumar, AS; Herrera, AF; Leung, J; Au, A; Chen, Y-Y; Moore, DH; Chen, DF; Hellawell, J; Wolverton, D; Hwang, ES; Hylton, NM
MLA Citation
Esserman, LJ, Kumar, AS, Herrera, AF, Leung, J, Au, A, Chen, Y-Y, Moore, DH, Chen, DF, Hellawell, J, Wolverton, D, Hwang, ES, and Hylton, NM. "Magnetic resonance imaging captures the biology of ductal carcinoma in situ." Journal of Clinical Oncology 24.28 (2006): 4603-4610.
PMID
17008702
Source
scival
Published In
Journal of Clinical Oncology
Volume
24
Issue
28
Publish Date
2006
Start Page
4603
End Page
4610
DOI
10.1200/JCO.2005.04.5518

Erratum: The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer (Annals of Surgical Oncology (September 2005) 12 (9) (705-711) DOI: 10.1245/ASO.2005.08.020)

Authors
Fan, Y-G; Tan, Y-Y; Wu, C-T; Treseler, P; Lu, Y; Chan, C-W; Hwang, S; Ewing, C; Esserman, L; Morita, E; Leong, SPL
MLA Citation
Fan, Y-G, Tan, Y-Y, Wu, C-T, Treseler, P, Lu, Y, Chan, C-W, Hwang, S, Ewing, C, Esserman, L, Morita, E, and Leong, SPL. "Erratum: The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer (Annals of Surgical Oncology (September 2005) 12 (9) (705-711) DOI: 10.1245/ASO.2005.08.020)." Annals of Surgical Oncology 12.11 (2005): 952--.
Source
scival
Published In
Annals of Surgical Oncology
Volume
12
Issue
11
Publish Date
2005
Start Page
952-
DOI
10.1245/ASO.2005.08.513

The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer

Background: Routine axillary lymph node dissection (ALND) after selective sentinel lymphadenectomy (SSL) in the treatment of breast cancer remains controversial. We sought to determine the need for routine ALND by exploring the relationship between sentinel lymph node (SLN) and non-SLN (NSLN) status. We also report our experience with disease relapse in the era of SSL and attempt to correlate this with SLN tumor burden. Methods: This was a retrospective study of 390 patients with invasive breast cancer treated at a single institution who underwent successful SSL from November 1997 to November 2002. Results: Of the 390 patients, 115 received both SSL and ALND. The percentage of additional positive NSLNs in the SLN-positive group (34.2%) was significantly higher than in the SLN-negative group (5.1%; P = .0004). The SLN macrometastasis group had a significantly higher rate of positive NSLNs (39.7%) compared with the SLN-negative group (5.1%; P = .0001). Sixteen patients developed recurrences during follow-up, including 6.1% of SLN-positive and 3.3% of SLN-negative patients. Among the SLN macrometastasis group, 8.7% had recurrence, compared with 2.2% of SLN micrometastases over a median follow-up period of 31.1 months. One regional failure developed out of 38 SLN-positive patients who did not undergo ALND. Conclusions: ALND is recommended for patients with SLN macrometastasis because of a significantly higher incidence of positive NSLNs. Higher recurrence rates are also seen in these patients. However, the role of routine ALND in patients with a low SLN tumor burden remains to be further determined by prospective randomized trials. © 2005 The Society of Surgical Oncology, Inc.

Authors
Fan, Y-G; Tan, Y-Y; Wu, C-T; Treseler, P; Lu, Y; Chan, C-W; Hwang, S; Ewing, C; Esserman, L; Morita, E; Leong, SPL
MLA Citation
Fan, Y-G, Tan, Y-Y, Wu, C-T, Treseler, P, Lu, Y, Chan, C-W, Hwang, S, Ewing, C, Esserman, L, Morita, E, and Leong, SPL. "The effect of sentinel node tumor burden on non-sentinel node status and recurrence rates in breast cancer." Annals of Surgical Oncology 12.9 (2005): 705-711.
PMID
16079953
Source
scival
Published In
Annals of Surgical Oncology
Volume
12
Issue
9
Publish Date
2005
Start Page
705
End Page
711
DOI
10.1245/ASO.2005.08.020

Primary tumor characteristics predict sentinel lymph node macrometastasis in breast cancer

Selective sentinel lymphadenectomy (SSL) is rapidly becoming the standard of care in the surgical management of patients with early breast cancer. Sentinel lymph node macrometastasis has been well documented in the literature to have a higher risk of nonsentinel node tumor involvement when compared to micrometastasis. The aim of our study was to determine the primary tumor characteristics associated with sentinel node macrometastasis that will allow us to preoperatively determine this subgroup of patients at risk. This study was a retrospective review of 644 patients who underwent successful SSL as part of their surgical treatment of breast cancer at the University of California San Francisco Carol Franc Buck Breast Care Center from November 1997 to August 2003. All patients underwent preoperative lymphoscintigraphy followed by wide excision or mastectomy and sentinel lymphadenectomy with or without axillary lymph node dissection. One hundred twenty-two patients had positive sentinel nodes on histology. Micrometastasis was present in 43 of these patients and macrometastasis in the remaining 79. Statistical analysis showed that a tumor size greater than 15 mm, poor tubule formation by the tumor cells, and lymphovascular invasion were significantly associated with sentinel node macrometastasis. A high mitotic count showed a trend but was not significant in our study. Patients with a tumor size greater than 15 mm, poor tubule formation, and lymphovascular invasion are at risk of having sentinel node macrometastasis. These patients can be identified preoperatively based on imaging and biopsy criteria, allowing the option of selective intraoperative pathologic evaluation of the sentinel node and immediate completion axillary dissection as necessary. © 2005 Blackwell Publishing, Inc.

Authors
Tan, Y-Y; Wu, C-T; Fan, Y-G; Hwang, S; Ewing, C; Lane, K; Esserman, L; Lu, Y; Treseler, P; Morita, E; Leong, SPL
MLA Citation
Tan, Y-Y, Wu, C-T, Fan, Y-G, Hwang, S, Ewing, C, Lane, K, Esserman, L, Lu, Y, Treseler, P, Morita, E, and Leong, SPL. "Primary tumor characteristics predict sentinel lymph node macrometastasis in breast cancer." Breast Journal 11.5 (2005): 338-343.
PMID
16174155
Source
scival
Published In
The Breast Journal
Volume
11
Issue
5
Publish Date
2005
Start Page
338
End Page
343
DOI
10.1111/j.1075-122X.2005.00043.x

Innovations in breast cancer care

PURPOSE: To examine the treatment of breast cancer from a historic perspective and explore current therapies and innovations in diagnosis and treatment. EPIDEMIOLOGY: In 2003, 212 600 new cases of breast cancer were diagnosed, and it is estimated that more than 40 000 of those cases will be fatal. The probability of developing invasive breast cancer is age-dependent, ranging from a 1 in 225 (0.44%) chance for women younger than 39 years to a 1 in 14 (7.02%) chance for women aged 60 through 79, with an overall 1 in 8 (12.83%) lifetime risk. REVIEW SUMMARY: From early in recorded history, women and their physicians have been plagued by breast cancer. Currently, breast cancer remains a leading cancer-related cause of death in women, second only to lung cancer. The treatment paradigm has shifted from one mandating radical excision of the breast and all surrounding tissue, to a more systemic view whereby as much breast tissue as possible is conserved and adjuvant therapy is offered to prevent metastasis. Advances in treatment have accelerated over the last few decades and have led and will continue to lead to significant improvements in mortality and morbidity. This article examines an approach to breast cancer management that considers the specific circumstances of each individual woman, guided by tumor biology, age, competing risks of death from other comorbidities, and personal preferences in which survivorship issues have assumed tremendous importance. Finally, future directions in breast cancer care are discussed. TYPE OF AVAILABLE EVIDENCE: Randomized-controlled trials, prospective cohort studies, systematic reviews. GRADE OF AVAILABLE EVIDENCE: Good to excellent. CONCLUSION: Physicians and patients now may select from a myriad of treatments for breast cancer, including surgery (mastectomy vs lumpectomy), radiation therapy, chemotherapy, hormonal therapy, and other biologically targeted therapies. In the future, molecular and imaging markers in combination with clinical parameters will help individually characterize breast cancer type, predict response to therapy, determine prognosis, and ultimately dictate the informed treatment choices women make in conjunction with their physicians.

Authors
Esserman, L; Lane, KT; Ewing, CA; Hwang, ES
MLA Citation
Esserman, L, Lane, KT, Ewing, CA, and Hwang, ES. "Innovations in breast cancer care." 2005. 294-305.
Source
scival
Volume
5
Publish Date
2005
Start Page
294
End Page
305

Ratio of positive to total number of sentinel nodes predicts nonsentinel node status in breast cancer patients

Selective sentinel lymphadenectomy (SSL) has replaced axillary lymph node dissection (ALND) for many patients with early breast cancer and negative sentinel lymph nodes (SLNs). Yet many patients with a positive SLN are undergoing unnecessary ALND, as no further disease is found in the axilla. The aim of our study was to determine factors associated with additional positive lymph nodes in the axilla in patients who have a positive SLN. This was a retrospective study of patients undergoing SSL with ALND as part of their treatment for breast cancer at a single institution from November 1997 to August 2003. Only patients with one or more positive SLNs were selected for this study. There were 86 patients who fit our study criteria. Of these, 38% had further positive lymph nodes upon ALND. More than one positive SLN and a ratio of positive SLNs to total SLNs of greater than 0.5 were found to be predictors for additional axillary nodal involvement in both univariate and multivariate analyses. The number of positive SLNs and the ratio of positive SLNs to total SLNs is an indication of total tumor burden in the sentinel nodes and may be a reflection of the propensity of the tumor for further lymphatic invasion in the axillary basin. © 2005 Blackwell Publishing, Inc.

Authors
Tan, Y-Y; Fan, Y-G; Lu, Y; Hwang, S; Ewing, C; Esserman, L; Morita, E; Treseler, P; Leong, SPL
MLA Citation
Tan, Y-Y, Fan, Y-G, Lu, Y, Hwang, S, Ewing, C, Esserman, L, Morita, E, Treseler, P, and Leong, SPL. "Ratio of positive to total number of sentinel nodes predicts nonsentinel node status in breast cancer patients." Breast Journal 11.4 (2005): 248-253.
PMID
15982390
Source
scival
Published In
Breast Journal
Volume
11
Issue
4
Publish Date
2005
Start Page
248
End Page
253
DOI
10.1111/j.1075-122X.2005.21633.x

MRI measurements of breast tumor volume predict response to neoadjuvant chemotherapy and recurrence-free survival

OBJECTIVE. The purpose of this study was to assess the value of MRI measurements of breast tumor size for predicting recurrence-free survival (RFS) in patients undergoing neoadjuvant (preoperative) chemotherapy and to compare the predictive value of MRI with that of established prognostic indicators. SUBJECTS AND METHODS. The study included 62 patients undergoing neoadjuvant chemotherapy. The longest diameter and volume of each tumor were measured on MRI before and after one and four cycles of treatment. Change in diameter on clinical examination, tumor size at pathology, and the number of positive nodes were determined. Each measure of tumor extent was assessed for the ability to predict RFS. RESULTS. Univariate Cox analysis showed initial MRI volume was the strongest predictor of RFS (p = 0.002). Final change in MRI volume (p = 0.015) was more predictive than change in diameter on MRI (p = 0.077) or clinical examination (p = 0.27). Initial diameter on MRI (p = 0.003) and clinical examination (p = 0.033), tumor size at pathology (p = 0.016), and number of positive nodes (p = 0.045) were also significantly predictive of RFS. Early change in MRI volume (p = 0.071) and diameter (p = 0.081) after one chemotherapy cycle showed trends of association with RFS. Multivariate analysis showed initial MRI volume (p = 0.005) and final change in MRI volume (p = 0.003) were significant independent predictors. CONCLUSION. MRI tumor volume was more predictive of RFS than tumor diameter, suggesting that volumetric changes measured using MRI may provide a more sensitive assessment of treatment efficacy. © American Roentgen Ray Society.

Authors
Partridge, SC; Gibbs, JE; Lu, Y; Esserman, LJ; Tripathy, D; Wolverton, DS; Rugo, HS; Hwang, ES; Ewing, CA; Hylton, NM
MLA Citation
Partridge, SC, Gibbs, JE, Lu, Y, Esserman, LJ, Tripathy, D, Wolverton, DS, Rugo, HS, Hwang, ES, Ewing, CA, and Hylton, NM. "MRI measurements of breast tumor volume predict response to neoadjuvant chemotherapy and recurrence-free survival." American Journal of Roentgenology 184.6 (2005): 1774-1781.
PMID
15908529
Source
scival
Published In
American Journal of Roentgenology
Volume
184
Issue
6
Publish Date
2005
Start Page
1774
End Page
1781

Clinical application of array-based comparative genomic hybridization to define the relationship between multiple synchronous tumors

Array-based comparative genomic hybridization (CGH) is a technique that allows genome wide screening of gains and losses in DNA copy number. In cases where multiple tumors are encountered, this genetic technique may prove useful in differentiating new primary tumors from recurrences. In this case report, we used array-based CGH to examine the genomic relationships among two leiomyosarcomas and two breast cancers in the same patient, three of which were diagnosed synchronously. Array-based CGH was performed on the four tumor samples using random prime amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within the tumors were compared and genetic alterations among the leiomyosarcomas and breast lesions were found. Overall, three distinct genetic profiles were observed. While the two leiomyosarcomas shared a similar pattern of genetic alterations, the two invasive breast lesions did not. The nearly identical pattern of genetic alterations belonging to the two metachronous leiomyosarcomas confirmed metastatic recurrence while the two different genetic profiles of the invasive ductal carcinomas suggest that the two lesions represented two distinct foci of multifocal disease rather than clonal extension of the primary tumor. We conclude that genetic analysis by array-based CGH can clearly elucidate the relationships between multiple tumors and may potentially serve as an important clinical tool. © 2005 USCAP, Inc All rights reserved..

Authors
Wa, CV; DeVries, S; Chen, YY; Waldman, FM; Hwang, ES
MLA Citation
Wa, CV, DeVries, S, Chen, YY, Waldman, FM, and Hwang, ES. "Clinical application of array-based comparative genomic hybridization to define the relationship between multiple synchronous tumors." Modern Pathology 18.4 (2005): 591-597.
PMID
15696129
Source
scival
Published In
Modern Pathology
Volume
18
Issue
4
Publish Date
2005
Start Page
591
End Page
597
DOI
10.1038/modpathol.3800332

Development of a novel method for measuring in vivo breast epithelial cell proliferation in humans

Cell proliferation plays an important role in all stages of carcinogenesis. Currently, no safe, direct, in vivo method of measuring breast epithelial cell (BEC) proliferation rates in humans exists. Static immunohistochemical markers of cell proliferation, such as Ki-67 and PCNA indices, have technical limitations including high inter-lab variability, inaccuracy in the presence of agents that cause G1/S cell cycle block and inadequate sensitivity in post-menopausal women with low BEC proliferation rates. We describe here a safe, direct method of measuring BEC proliferation rates in vivo in women using heavy water (2H2O) labeling coupled with mass spectrometric analysis. Proliferation of normal and tumor BEC was measured from breast tissue biopsies in women undergoing mastectomy (n=11) and normal BEC from healthy volunteers (n=16). Women took heavy water (50-150 ml per day) for 1-4 weeks. Pre-menopausal women had significantly higher proliferation rates than post-menopausal women (0.7 ± 0.1 versus 0.2 ± 0.1 new cells per day, respectively), and tumor BEC had different proliferation rates than normal BEC from the same breast. The method is analytically reproducible and remains sensitive in the range of low proliferation rates. In summary, this novel method of measuring BEC proliferation in vivo holds promise for assessing the effects of anti-proliferative chemopreventive and chemotherapeutic agents. © Springer 2005.

Authors
Misell, LM; Hwang, ES; Au, A; Esserman, L; Hellerstein, MK
MLA Citation
Misell, LM, Hwang, ES, Au, A, Esserman, L, and Hellerstein, MK. "Development of a novel method for measuring in vivo breast epithelial cell proliferation in humans." Breast Cancer Research and Treatment 89.3 (2005): 257-264.
PMID
15754124
Source
scival
Published In
Breast Cancer Research and Treatment
Volume
89
Issue
3
Publish Date
2005
Start Page
257
End Page
264
DOI
10.1007/s10549-004-2228-5

Array-based comparative genomic hybridization from formalin-fixed, paraffin-embedded breast tumors

Identification of prognostic and predictive genomic markers requires long-term clinical follow-up of patients. Extraction of high-quality DNA from archived formalin-fixed, paraffin-embedded material is essential for such studies. Of particular importance is a robust reproducible method of whole genome amplification for small tissue samples. This is especially true for high-resolution analytical approaches because different genomic regions and sequences may amplify differentially. We have tested a number of protocols for DNA amplification for array-based comparative genomic hybridization (CGH), in which relative copy number of the entire genome is measured at 1 to 2 mb resolution. Both random-primed amplification and degenerate oligonucleotide-primed amplification approaches were tested using varying amounts of fresh and paraffin-extracted normal and breast tumor input DNAs. We found that random-primed amplification was clearly superior to degenerate oligonucleotide-primed amplification for array-based CGH. The best quality and reproducibility strongly depended on accurate determination of the amount of input DNA using a quantitative polymerase chain reaction-based method. Reproducible and high-quality results were attained using 50 ng of input DNA, and some samples yielded quality results with as little as 5 ng input DNA. We conclude that random-primed amplification of DNA isolated from paraffin sections is a robust and reproducible approach for array-based CGH analysis of archival tumor samples. Copyright © American Society for Investigative Pathology and the Association for Molecular Pathology.

Authors
DeVries, S; Nyante, S; Korkola, J; Segraves, R; Nakao, K; Moore, D; Bae, H; Wilhelm, M; Hwang, S; Waldman, F
MLA Citation
DeVries, S, Nyante, S, Korkola, J, Segraves, R, Nakao, K, Moore, D, Bae, H, Wilhelm, M, Hwang, S, and Waldman, F. "Array-based comparative genomic hybridization from formalin-fixed, paraffin-embedded breast tumors." Journal of Molecular Diagnostics 7.1 (2005): 65-71.
PMID
15681476
Source
scival
Published In
Journal of Molecular Diagnostics
Volume
7
Issue
1
Publish Date
2005
Start Page
65
End Page
71
DOI
10.1016/S1525-1578(10)60010-4

Safety of immediate transverse rectus abdominis myocutaneous breast reconstruction for patients with locally advanced disease

Hypothesis: Immediate transverse rectus abdominis myocutaneous breast reconstruction combined with post-operative radiation therapy after mastectomy is safe and effective. Design: Retrospective case series. Setting: University-based teaching hospital. Patients: From January 1, 1996, through December 31, 2003, 252 patients underwent mastectomy and immediate transverse rectus abdominis myocutaneous flap reconstruction. Of those, 35 patients received postoperative radiation therapy (stage 1, n= 1; II, n= 17; III, n= 15; IV, n= 2). Age range was 29 to 72 years (mean, 49.5 years). Follow-up was 1 to 8 years (mean, 48 months). Main Outcome Measures: Flap loss, fat necrosis, flap volume loss, adjuvant treatment delay, and need for additional surgery. Recults: The rate of flap survival was 100%. Median operative time was 5.5 hours. Average hospital stay was 5.2 days. Fat necrosis occurred in 3 patients, with volume loss requiring additional surgery in 2 patients (6%). Post-operative adjuvant therapy was not significantly delayed (median interval, 32 days). With a median follow-up of 48 months, local recurrence was present in only 1 patient (3%), who underwent successful local salvage, and distant metastasis occurred in 4 patients (11%). Conclusions: Immediate transverse rectus abdominis myocutaneous breast reconstruction followed by radiation therapy is safe, with minimal morbidity and no significant change in tissue volume. Complications tend to be minor, not delaying adjuvant therapy. Immediate breast reconstruction should be considered after mastectomy, despite the need for postoperative radiation therapy.

Authors
Foster, RD; Hansen, SL; Esserman, LJ; Hwang, ES; Ewing, C; Lane, K; Anthony, JP
MLA Citation
Foster, RD, Hansen, SL, Esserman, LJ, Hwang, ES, Ewing, C, Lane, K, and Anthony, JP. "Safety of immediate transverse rectus abdominis myocutaneous breast reconstruction for patients with locally advanced disease." Archives of Surgery 140.2 (2005): 196-200.
PMID
15724003
Source
scival
Published In
Archives of Surgery
Volume
140
Issue
2
Publish Date
2005
Start Page
196
End Page
200
DOI
10.1001/archsurg.140.2.196

Surgical management of hepatic breast cancer metastases: Commentary

Authors
Golshan, M; Iglehart, JD; Hwang, ES; Esserman, LJ; Kooby, DA
MLA Citation
Golshan, M, Iglehart, JD, Hwang, ES, Esserman, LJ, and Kooby, DA. "Surgical management of hepatic breast cancer metastases: Commentary." ONCOLOGY 19.12 (2005): 1587-1596.
Source
scival
Published In
Oncology
Volume
19
Issue
12
Publish Date
2005
Start Page
1587
End Page
1596

Internal mammary sentinel lymph node mapping for invasive breast cancer: Implications for staging and treatment

The optimal staging and treatment of the internal mammary nodes (IMNs) among patients with invasive breast cancer (IBC) is controversial. Although medial tumors have been reported to more commonly drain to IMNs, other variables predictive for IMN drainage may help identify those patients who may benefit from further IMN assessment. Factors associated with IMN drainage were analyzed among 141 patients who underwent lymphatic mapping and selective sentinel lymphadenectomy using intradermal injection (ID) or peritumoral (PT) injection. Fourteen of 83 patients (17%) receiving PT injections had IMN drainage, compared to none among the 58 patients who underwent ID injection alone (p = 0.0004). There were no differences in patient or tumor variables detected between the two groups. Among patients receiving PT injections, no factors examined were significantly associated with IMN drainage on univariate analysis. Using the multivariate logistic regression model, palpable disease was the most important factor associated with IMN drainage (risk ratio [RR] = 6.02; 95% confidence interval [CI] 0.64-56.34; p = 0.05). In addition, lymphatic/vascular invasion (LVI) and age less than 50 years were associated with IMN drainage (RR = 6.17; 95% CI 1.02-37.50; p = 0.09 and RR = 2.94; 95% CI 0.82-10.49; p = 0.09, respectively). IMN drainage occurred in a significant proportion of patients after PT injection, but not ID injection. In the final model, palpable disease was the most important factor associated with IMN drainage; LVI and age less than 50 years were of borderline significance. These factors may aid in the selection of patients who might benefit from further staging or treatment of the IMNs.

Authors
Park, C; Seid, P; Morita, E; Iwanaga, K; Weinberg, V; Quivey, J; Hwang, ES; Esserman, LJ; Leong, SPL
MLA Citation
Park, C, Seid, P, Morita, E, Iwanaga, K, Weinberg, V, Quivey, J, Hwang, ES, Esserman, LJ, and Leong, SPL. "Internal mammary sentinel lymph node mapping for invasive breast cancer: Implications for staging and treatment." Breast Journal 11.1 (2005): 29-33.
PMID
15647075
Source
scival
Published In
The Breast Journal
Volume
11
Issue
1
Publish Date
2005
Start Page
29
End Page
33
DOI
10.1111/j.1075-122X.2005.21527.x

Risk factors for estrogen receptor-positive breast cancer

Hypothesis: Some risk factors associated with breast cancer may be more predictive of estrogen receptor (ER)-positive than ER-negative tumors. Design: Survey of patients enrolled in a study of breast cancer risk factors. Setting: Community population in a northern California county. Patients: A total of 234 individuals diagnosed as having breast cancer between July 1, 1997, and June 30, 1999, reporting Marin County, California, residence and participating in a questionnaire regarding exposure to breast cancer risk factors. Main Outcome Measure: Diagnosis of ER-positive vs ER-negative breast cancer. Results: Comparison between ER-positive and ER-negative cases showed several factors predictive of ER-positive tumors. In a multivariate model, years of hormone therapy use remained the most significant predictor of ER-positive disease. Conclusions: Patients diagnosed as having ER-positive breast cancer were more likely to have undergone hormone therapy. The excess of ER-positive breast cancers reported in Marin County could, therefore, in part, be related to hormone therapy.

Authors
Hwang, ES; Chew, T; Shiboski, S; Farren, G; Benz, CC; Wrensch, M
MLA Citation
Hwang, ES, Chew, T, Shiboski, S, Farren, G, Benz, CC, and Wrensch, M. "Risk factors for estrogen receptor-positive breast cancer." Archives of Surgery 140.1 (2005): 58-62.
PMID
15655207
Source
scival
Published In
Archives of Surgery
Volume
140
Issue
1
Publish Date
2005
Start Page
58
End Page
62
DOI
10.1001/archsurg.140.1.58

Accuracy of selective sentinel lymphadenectomy after neoadjuvant chemotherapy: Effect of clinical node status at presentation

Both neoadjuvant chemotherapy and selective sentinel lymphadenectomy (SSL) are increasingly being used in treating primary breast cancer. It is important to determine whether SSL can be used after neoadjuvant chemotherapy and whether clinical node status at presentation affects accuracy of SSL. Between 1995 and 2003, 53 evaluable cases of invasive breast cancer were treated with neoadjuvant chemotherapy followed by SSL and completion axillary node dissection. The accuracy of SSL and the number of failed SSLs were assessed in the entire group and in the subset that were clinically node positive at presentation. The sensitivity of SSL was 96%, the negative predictive value was 96%, and the sentinel node identification rate was 94%. Of the 53 evaluable patients, 23 had clinically node-positive disease at presentation (43%) and the remainder were clinically node negative (57%). Of the successfully completed SSL, the status of the sentinel lymph node corresponded to that of overall axillary status in 49 of 50 patients (accuracy rate 98%). Two of the 23 patients with clinically node-positive disease at presentation had unsuccessful SSL. Of the remaining 21 patients with a clinically positive axilla before systemic therapy, a false-negative SSL result occurred in 1 patient (accuracy 95%, sensitivity 91%). Selective sentinel lymphadenectomy after neoadjuvant chemotherapy is both feasible and accurate. Although early reports found a lower performance of SSL after neoadjuvant chemotherapy, this study suggests reevaluation of the current practice of full axillary lymph node dissection in this setting, particularly in those patients who are clinically node negative at presentation. © 2004 by the American College of Surgeons.

Authors
Lang, JE; Esserman, LJ; Ewing, CA; Rugo, HS; Lane, KT; Leong, SP; Hwang, ES
MLA Citation
Lang, JE, Esserman, LJ, Ewing, CA, Rugo, HS, Lane, KT, Leong, SP, and Hwang, ES. "Accuracy of selective sentinel lymphadenectomy after neoadjuvant chemotherapy: Effect of clinical node status at presentation." Journal of the American College of Surgeons 199.6 (2004): 856-862.
PMID
15555967
Source
scival
Published In
Journal of The American College of Surgeons
Volume
199
Issue
6
Publish Date
2004
Start Page
856
End Page
862
DOI
10.1016/j.jamcollsurg.2004.08.023

Patterns of chromosomal alterations in breast ductal carcinoma in situ

Purpose: Ductal carcinoma in situ (DCIS) is thought to be a nonobligate precursor of invasive cancer. Genomic changes specific to pure DCIS versus invasive cancer, as well as alterations unique to individual DCIS subtypes, have not been fully defined. Experimental Design: Chromosomal copy number alterations were examined by comparative genomic hybridization in 34 cases of pure DCIS and compared with 12 cases of paired synchronous DCIS and invasive ductal cancer, as well as to 146 additional cases of invasive breast cancer of ductal or lobular histology. Genomic differences between high-grade and low/intermediate-grade DCIS, as well as between pure DCIS and invasive cancer, were identified. Results: Pure DCIS showed almost the same degree of chromosomal instability as invasive ductal cancers. A higher proportion of low/intermediate-grade versus high-grade DCIS had loss of 16q (65 versus 12%, respectively; P = 0.002). When compared with lower grade DCIS, high-grade DCIS exhibited more frequent gain of 17q (65 versus 41%; P = 0.15) and higher frequency loss of 8p (77 versus 41%; P = 0.0.1). Chromosomal alterations in those cases with synchronous DCIS and invasive ductal cancer showed a high degree of shared changes within the two components. Conclusions: DCIS is genetically advanced, showing a similar degree of chromosomal alterations as invasive ductal cancer. The pattern of alterations differed between high- and low/intermediate-grade DCIS, supporting a model in which different histological grades of DCIS are associated with distinct genomic changes. These regions of chromosomal alterations may be potential targets for treatment and/or markers of prognosis.

Authors
Hwang, ES; DeVries, S; Chew, KL; II, DHM; Kerlikowske, K; Thor, A; Ljung, B-M; Waldman, FM
MLA Citation
Hwang, ES, DeVries, S, Chew, KL, II, DHM, Kerlikowske, K, Thor, A, Ljung, B-M, and Waldman, FM. "Patterns of chromosomal alterations in breast ductal carcinoma in situ." Clinical Cancer Research 10.15 (2004): 5160-5167.
PMID
15297420
Source
scival
Published In
Clinical Cancer Research
Volume
10
Issue
15
Publish Date
2004
Start Page
5160
End Page
5167
DOI
10.1158/1078-0432.CCR-04-0165

Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma

BACKGROUND. Lobular carcinoma in situ (LCIS) of the breast is considered a marker for an increased risk of carcinoma in both breasts. However, the frequent association of LCIS with invasive lobular carcinoma (ILC) suggests a precursor-product relation. The possible genomic relation between synchronous LCIS and ILC was analyzed using the technique of array-based comparative genomic hybridization (CGH). METHODS. Twenty-four samples from the University of California-San Francisco pathology archives that contained synchronous LCIS and ILC were identified. Array CGH was performed using random primer-amplified microdissected DNA. Samples were hybridized onto bacterial artificial chromosome arrays composed of approximately 2400 clones. Patterns of alterations within synchronous LCIS and ILC were compared. RESULTS. A substantial proportion of the genome was altered in samples of both LCIS and ILC. The most frequent alterations were gain of 1q and loss of 16q, both of which usually occurred as whole-arm changes. Smaller regions of gain and loss were seen on other chromosome arms. Fourteen samples of LCIS were related more to their paired samples of ILC than to any other ILC, as demonstrated by a weighted similarity score. CONCLUSIONS. LCIS and ILC are neoplastic lesions that demonstrate a range of genomic alterations. In the current study, the genetic relation between synchronous LCIS and ILC suggested clonality in a majority of the paired specimens. These data were consistent with a progression pathway from LCIS to ILC. The authors conclude that LCIS, which is known to be a marker for an environment that is permissive of neoplasia, may itself represent a precursor to invasive carcinoma. © 2004 American Cancer Society.

Authors
Hwang, ES; Nyante, SJ; Chen, YY; Moore, D; DeVries, S; Korkola, JE; Esserman, LJ; Waldman, FM
MLA Citation
Hwang, ES, Nyante, SJ, Chen, YY, Moore, D, DeVries, S, Korkola, JE, Esserman, LJ, and Waldman, FM. "Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma." Cancer 100.12 (2004): 2562-2572.
PMID
15197797
Source
scival
Published In
Cancer
Volume
100
Issue
12
Publish Date
2004
Start Page
2562
End Page
2572
DOI
10.1002/cncr.20273

Applying the neoadjuvant paradigm to ductal carcinoma in situ.

Local treatment options for ductal carcinoma in situ (DCIS) are virtually identical to those for early invasive breast cancer, despite the fact that the survival from this condition is much higher. Our ability to more appropriately tailor therapy for DCIS is hampered by a lack of understanding of the natural history of DCIS, our limited ability to predict the rate of progression to invasive cancer and the response to therapy, and the absence of tools to follow patients who have not had invasive treatments. Neoadjuvant therapy, which has been proven to be both safe and effective in tailoring treatments for invasive cancer, could be ideally suited to DCIS. However, neoadjuvant therapy requires that doctors and patients delay surgical treatment that has known benefits. In order to successfully introduce this approach into clinical practice, risk assessment and decision support tools will be needed to help physicians and patients feel comfortable that they are not being exposed to unnecessary or excessive risk. In addition, we need better imaging to track extent and progression of disease. Among the possible benefits of the neoadjuvant approach, we may discover that many lesions are responsive and some even reversible, leaving us with treatments that might be tailored to biology and with important clues for breast cancer prevention in high-risk women.

Authors
Esserman, L; Sepucha, K; Ozanne, E; Hwang, ES
MLA Citation
Esserman, L, Sepucha, K, Ozanne, E, and Hwang, ES. "Applying the neoadjuvant paradigm to ductal carcinoma in situ." Annals of surgical oncology : the official journal of the Society of Surgical Oncology 11.1 Suppl (2004): 28S-36S.
PMID
15015707
Source
scival
Published In
Annals of surgical oncology : the official journal of the Society of Surgical Oncology
Volume
11
Issue
1 Suppl
Publish Date
2004
Start Page
28S
End Page
36S

Array-based comparative genomic hybridization of ductal carcinoma in situ and synchronous invasive lobular cancer

It has been increasingly recognized that ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and invasive cancer of the breast are often closely associated with one another. However, the genomic relationship between these histologically distinct entities has not been well characterized. Refinements in high-resolution comparative genomic hybridization (CGH) techniques allow for a detailed comparison of genomic alterations in synchronously occurring tumors. The following case illustrates how array CGH may be used to better understand whether synchronous neoplasms share a common orgin. © 2004 Elsevier Inc. All rights reserved.

Authors
Nyante, SJ; Devries, S; Chen, YY; Hwang, ES
MLA Citation
Nyante, SJ, Devries, S, Chen, YY, and Hwang, ES. "Array-based comparative genomic hybridization of ductal carcinoma in situ and synchronous invasive lobular cancer." Human Pathology 35.6 (2004): 759-763.
PMID
15188144
Source
scival
Published In
Human Pathology
Volume
35
Issue
6
Publish Date
2004
Start Page
759
End Page
763
DOI
10.1016/j.humpath.2003.11.009

Neoadjuvant hormonal therapy for ductal carcinoma in situ: trial design and preliminary results.

For some women, the treatment for ductal carcinoma in situ (DCIS) may be even more aggressive than treatments undertaken for early-stage invasive disease. Expectant management is not a tenable alternative, given that in a significant percentage of patients, DCIS eventually progresses to invasive cancer. Nevertheless, if this progression could be halted or reversed with primary medical therapy alone, a significant portion of the 50,000 women diagnosed with DCIS in the United States annually could potentially avoid the morbidity of surgery and radiation for this disease. The most promising therapeutic candidates in this regard are those treatments targeting hormone receptors on breast cancer cells. We have initiated a clinical trial of neoadjuvant hormonal therapy for women with hormone receptor-positive DCIS. We discuss the clinical rationale and study design for this trial and present our preliminary results.

Authors
Hwang, ES; Esserman, L
MLA Citation
Hwang, ES, and Esserman, L. "Neoadjuvant hormonal therapy for ductal carcinoma in situ: trial design and preliminary results." Annals of surgical oncology : the official journal of the Society of Surgical Oncology 11.1 Suppl (2004): 37S-43S.
PMID
15015708
Source
scival
Published In
Annals of surgical oncology : the official journal of the Society of Surgical Oncology
Volume
11
Issue
1 Suppl
Publish Date
2004
Start Page
37S
End Page
43S

Integrative tumor board: recurrent breast cancer or new primary? UCSF Osher Center for Integrative Medicine and UCSF Carol Franc Buck Breast Care Center.

Authors
Jacobs, BP; Burns, B; Marya, R; Chapman, J; Stone, B; Hwang, S; Goldman, M; Barrows, K; Hamolsky, D; Sampel, K
MLA Citation
Jacobs, BP, Burns, B, Marya, R, Chapman, J, Stone, B, Hwang, S, Goldman, M, Barrows, K, Hamolsky, D, and Sampel, K. "Integrative tumor board: recurrent breast cancer or new primary? UCSF Osher Center for Integrative Medicine and UCSF Carol Franc Buck Breast Care Center." Integrative cancer therapies 2.3 (2003): 289-300.
PMID
15035894
Source
scival
Published In
Integrative cancer therapies
Volume
2
Issue
3
Publish Date
2003
Start Page
289
End Page
300

Differentiation of Lobular versus Ductal Breast Carcinomas by Expression Microarray Analysis

Invasive lobular and ductal breast tumors have distinct histologies and clinical presentation. Other than altered expression of E-cadherin, little is known about the underlying biology that distinguishes the tumor subtypes. We used cDNA microarrays to identify genes differentially expressed between lobular and ductal tumors. Unsupervised clustering of tumors failed to distinguish between the two subtypes. Prediction analysis for microarrays (PAM) was able to predict tumor type with an accuracy of 93.7%. Genes that were significantly differentially expressed between the two groups were identified by MaxT permutation analysis using t tests (20 cDNA clones and 10 unique genes), significance analysis for microarrays (33 cDNA clones and 15 genes, at an estimated false discovery rate of 2%), and PAM (31 cDNAs and 15 genes). There were 8 genes identified by all three of these related methods (E-cadherin, survivin, cathepsin B, TPI1, SPRY1, SCYA14, TFAP2B, and thrombospondin 4), and an additional 3 that were identified by significance analysis for microarrays and PAM (osteopontin, HLA-G, and CHC1). To validate the differential expression of these genes, 7 of them were tested by real-time quantitative PCR, which verified that they were differentially expressed in lobular versus ductal tumors. In conclusion, specific changes in gene expression distinguish lobular from ductal breast carcinomas. These genes may be important in understanding the basis of phenotypic differences among breast cancers.

Authors
Korkola, JE; DeVries, S; Fridlyand, J; Hwang, ES; Estep, ALH; Chen, Y-Y; Chew, KL; Dairkee, SH; Jensen, RM; Waldman, FM
MLA Citation
Korkola, JE, DeVries, S, Fridlyand, J, Hwang, ES, Estep, ALH, Chen, Y-Y, Chew, KL, Dairkee, SH, Jensen, RM, and Waldman, FM. "Differentiation of Lobular versus Ductal Breast Carcinomas by Expression Microarray Analysis." Cancer Research 63.21 (2003): 7167-7175.
PMID
14612510
Source
scival
Published In
Cancer Research
Volume
63
Issue
21
Publish Date
2003
Start Page
7167
End Page
7175

Failure to harvest sentinel lymph nodes identified by preoperative lymphoscintigraphy in breast cancer patients

Selective sentinel lymphadenectomy dissection has been demonstrated to have high predictive value for axillary staging in breast cancer patients. Preoperative lymphoscintigraphy can localize and facilitate the harvesting of sentinel lymph nodes (SNLs) with a high success rate. The failure rate of selective sentinel lymphodenectomy ranges between 2% and 8%. Details of the failures were seldom addressed. This study analyzes the causes of failure to harvest SLNs in spite of positive preoperative lymphoscintigraphy. From November 1997 through November 2000, 201 female patients with histologically confirmed and operable breast carcinoma underwent selective sentinel lymphadenectomy at the University of California, San Francisco (UCSF) Carol Franc Buck Breast Care Center. Among these patients, 183 (91%) received preoperative lymphoscintigraphy to identify axillary lymph nodes. The causes of failure to harvest the SLNs in this group of patients despite successful preoperative lymphoscintigraphy were analyzed. In our series, the failure rate of SLN identification was 7.0% (14/201). The failure rate for our first year was 11.1% (6/54), second year 9.1% (7/77), and third year 1.4% (1/70). The incidence of failure in spite of positive preoperative lymphoscintigraphy was 3.5% (6/170). The shine-through effect of the primary injection site and failure to visualize a blue lymph node were the main reasons for technical failure. Most of these cases occurred during our learning curve of the procedure. The possibility of failure to get the SLN should be explained to patients before surgery. Axillary lymph node dissection (ALND) should be done if selective SLN dissection is not successful.

Authors
Wu, C-T; Morita, ET; Treseler, PA; Esserman, LJ; Hwang, ES; Kuerer, HM; Santos, CL; Leong, SPL
MLA Citation
Wu, C-T, Morita, ET, Treseler, PA, Esserman, LJ, Hwang, ES, Kuerer, HM, Santos, CL, and Leong, SPL. "Failure to harvest sentinel lymph nodes identified by preoperative lymphoscintigraphy in breast cancer patients." Breast Journal 9.2 (2003): 86-90.
PMID
12603380
Source
scival
Published In
Breast Journal
Volume
9
Issue
2
Publish Date
2003
Start Page
86
End Page
90
DOI
10.1046/j.1524-4741.2003.09205.x

Magnetic resonance imaging in patients diagnosed with ductal carcinoma-in-situ: Value in the diagnosis of residual disease, occult invasion, and multicentricity

Background: Although magnetic resonance imaging (MRI) has been shown to be a sensitive imaging tool for invasive breast cancers, its utility in ductal carcinoma-in-situ (DCIS) of the breast remains controversial. We studied the performance of MRI in patients with known DCIS for assessment of residual disease, occult invasion, and multicentricity to determine the clinical role of MRI in this setting. Methods: Fifty-one patients with biopsy-proven DCIS underwent contrast-enhanced MRI before surgical treatment. Pre-, early post-, and late postcontrast three-dimensional gradient echo images were obtained and MRI findings were correlated with histopathology. When possible, the performance of MRI and mammography was compared. Results: The accuracy of MRI was 88% in predicting residual disease, 82% in predicting invasive disease, and 90% in predicting multicentricity. The performance of MRI was equivalent in the core biopsy group when compared with the surgical biopsy group. For occult invasion only, MRI and mammography were equivalent. However, overall, MRI was more sensitive and had a higher negative predictive value than mammography. Conclusions: MRI of DCIS can serve as a useful adjunct to mammography by providing a more accurate assessment of the extent of residual or multicentric disease. The performance of MRI is not significantly affected by antecedent surgical excision. MRI may be particularly valuable if preoperatively negative. © 2003 The Society of Surgical Oncology, Inc.

Authors
Hwang, ES; Kinkel, K; Esserman, LJ; Lu, Y; Weidner, N; Hylton, NM
MLA Citation
Hwang, ES, Kinkel, K, Esserman, LJ, Lu, Y, Weidner, N, and Hylton, NM. "Magnetic resonance imaging in patients diagnosed with ductal carcinoma-in-situ: Value in the diagnosis of residual disease, occult invasion, and multicentricity." Annals of Surgical Oncology 10.4 (2003): 381-388.
PMID
12734086
Source
scival
Published In
Annals of Surgical Oncology
Volume
10
Issue
4
Publish Date
2003
Start Page
381
End Page
388
DOI
10.1245/ASO.2003.03.085

Skin-sparing mastectomy and immediate breast reconstruction: A prospective cohort study for the treatment of advanced stages of breast carcinoma

Background: Recent published series demonstrate the safety and effectiveness of skin-sparing mastectomy (SSM) with immediate reconstruction for the treatment of early-stage breast carcinoma. Although several reports have retrospectively evaluated outcomes after breast reconstruction for locally advanced disease (stages IIB and III), no study has specifically considered immediate breast reconstruction after SSM for locally advanced disease. Methods: From 1996 to 1998, 67 consecutive patients with breast carcinoma underwent SSM with immediate reconstruction and were prospectively observed. From this group of patients, those with locally advanced disease (stage IIB, n = 12; stage III, n = 13) were analyzed separately. Tumor characteristics, adjuvant therapy, type of reconstruction, operative time, complications, hospital stay, and incidence of local recurrence and distant metastasis were noted. Results: Breast reconstruction consisted of a transverse rectus abdominis myocutaneous flap (n = 22) or a latissimus flap plus an implant (n = 4). The median operative time was 5.5 hours; the average hospital stay was 5.2 days. Complications required reoperation in three patients (12%): partial skin flap necrosis in two and partial abdominal skin necrosis in one. Surgery on the opposite breast for symmetry was required in one patient (4%). Postoperative adjuvant therapy was not significantly delayed (median interval, 32 days). With a median length of follow-up of 49.2 months (range, 33-64 months), local recurrence was present in only one patient (4%), with successful local salvage treatment, and distant metastasis was present in four patients (16%). Conclusions: SSM with immediate reconstruction seems safe and effective and has a low morbidity for patients with advanced stages of breast carcinoma. Local recurrence rates and the incidence of distant metastasis are not increased compared with those of patients who have had modified radical mastectomies without reconstruction.

Authors
Foster, RD; Esserman, LJ; Anthony, JP; Hwang, E-SS; Do, H
MLA Citation
Foster, RD, Esserman, LJ, Anthony, JP, Hwang, E-SS, and Do, H. "Skin-sparing mastectomy and immediate breast reconstruction: A prospective cohort study for the treatment of advanced stages of breast carcinoma." Annals of Surgical Oncology 9.5 (2002): 462-466.
PMID
12052757
Source
scival
Published In
Annals of Surgical Oncology
Volume
9
Issue
5
Publish Date
2002
Start Page
462
End Page
466
DOI
10.1245/aso.2002.9.5.462

Analysis of bone marrow micrometastasis in primary breast cancer: Automated cellular imaging analysis in relation to quantitative RT-PCR and tumor clinicopathologic features

The presence of bone marrow micrometastasis (MM) has been reported to be an adverse prognostic indicator in primary breast cancer, and may be of value in adjuvant therapy decision-making. To date, MM detection has been pursued by a variety of cell-based and molecular methods, and it remains unclear which methodologies are most useful, including recently developed techniques. In a prospective study, we have evaluated MM using novel methods applied to primary breast cancer patients. Methods: We have developed and optimized a highly sensitive cell-based MM assay (cMM) involving multiple antigen immunomagnetic capture (positive selection for MM), anti-cytokeratin immunocytochemical (ICC) staining, and automated cellular imaging (ACIS, ChromaVision Medical Systems, Inc.). The resulting cellular images are immediately available for review by laboratory professionals and pathologists. In addition to this assay, we have developed quantitative RT-PCR for MM-associated mRNAs mammaglobin, PSA, HER2, alternatively spliced HER2, and EGFRvIII. Results: The ICC-based assay has been documented to provide reproducible detection and enumeration of rare carcinoma cells (lte] 1 MM per 10e8 mononuclear cells). Initial results from 21 consecutive cases analyzed using the cMM assay detected marrow MM in 10/21 (48%) of specimens. MM in matched blood samples were frequently detected but generally at lower levels. Quantitative RT-PCR has been performed on 165 patient marrow samples, including all 21 analyzed by the ICC-based assay. RT-PCR assays detected MM in 10-20% of patients depending upon target gene. Results did not correlate closely with each other or with the ICC-based assay. Updated results will be presented, along with correlations with clinicopathologic parameters including tumor size, grade, nodal status, and primary tumor ER/PR/HER2 results.Conclusions: This prospective study compares recently developed and highly sensitive molecular and cell-based methods for MM analysis. Understanding performance differences of new methods should enhance both our understanding of the biology of MM and facilitate the assessment of MM assay(s)in clinical settings.

Authors
Park, JW; Scott, JH; Hwang, ES; Esserman, LJ; Bauer, KD; Bossy, B
MLA Citation
Park, JW, Scott, JH, Hwang, ES, Esserman, LJ, Bauer, KD, and Bossy, B. "Analysis of bone marrow micrometastasis in primary breast cancer: Automated cellular imaging analysis in relation to quantitative RT-PCR and tumor clinicopathologic features." Breast Cancer Research and Treatment 69.3 (January 1, 2001): 259-.
Source
scopus
Published In
Breast Cancer Research and Treatment
Volume
69
Issue
3
Publish Date
2001
Start Page
259

Genomic alterations in tubular breast carcinomas

Tubular carcinoma of the breast is a well-differentiated variant of invasive ductal carcinoma and has been shown to have an exceptionally favorable prognosis, as manifested by a low incidence of lymph node metastases and an excellent overall survival. It is unknown whether this subtype represents an early step along the continuum of development to a more aggressive, poorly differentiated ductal cancer, or whether these cancers are destined to remain well differentiated with limited metastatic potential. We undertook an analysis of 18 pure tubular carcinomas of the breast using comparative genomic hybridization to evaluate the chromosomal changes in these tumors. An average of 3.6 chromosomal alterations of the genome were identified per case. The most frequent change involved loss of 16q (in 78% of tumors) and gain of 1q (in 50% of tumors). All but one case with 1q gain also exhibited a concomitant 16q loss. Other frequent changes involved 16p gain in 7 of 18 cases (39%) and distal 8p loss in 5 of 18 cases (28%). Comparison with known genomic alterations in a mixed group of invasive cancers shows tubular cancer to have fewer overall chromosomal changes per tumor (P < .01), higher frequency of 16q loss (P < .001), and lower frequency of 17p loss (P = .007). These results strongly suggest that tubular carcinomas are a genetically distinct group of breast cancers. Copyright © 2001 by W.B. Saunders Company.

Authors
Waldman, FM; Hwang, ES; Etzell, J; Eng, C; DeVries, S; Bennington, J; Thor, A
MLA Citation
Waldman, FM, Hwang, ES, Etzell, J, Eng, C, DeVries, S, Bennington, J, and Thor, A. "Genomic alterations in tubular breast carcinomas." Human Pathology 32.2 (2001): 222-226.
Source
scival
Published In
Human Pathology
Volume
32
Issue
2
Publish Date
2001
Start Page
222
End Page
226
DOI
10.1053/hupa.2001.21564

MRI phenotype is associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer

Background: The preferred management for women with stage II or locally advanced breast cancer (LABC) is neoadjuvant chemotherapy. Pathologic response to chemotherapy has been shown to be an excellent predictor of outcome. Surrogates that can predict pathologic response and outcome will fuel future changes in management. Magnetic resonance imaging (MRI) demonstrates that patients with LABC have distinct tumor patterns. We investigated whether or not these patterns predict response to therapy. Methods: Thirty-three women who received neoadjuvant doxorubicin and cyclophosphamide chemotherapy for 4 cycles and serial breast MRI scans before and after therapy were evaluated for this study. Response to therapy was measured by change in the longest diameter on the MRI. Results: Five distinct imaging patterns were identified: circumscribed mass, nodular tissue infiltration diffuse tissue infiltration, patchy enhancement, and septal spread. The likelihood of a partial or complete response as measured by change in longest diameter was 77%, 37.5%, 20%, and 25%, respectively. Conclusions: MRI affords three-dimensional characterization of tumors and has revealed distinct patterns of tumor presentation that predict response. A multisite trial is being planned to combine imaging and genetic information in an effort to better understand and predict response and, ultimately, to tailor therapy and direct the use of novel agents.

Authors
Esserman, L; Kaplan, E; Partridge, S; Tripathy, D; Rugo, H; Park, J; Hwang, S; Kuerer, H; Sudilovsky, D; Lu, Y; Hylton, N
MLA Citation
Esserman, L, Kaplan, E, Partridge, S, Tripathy, D, Rugo, H, Park, J, Hwang, S, Kuerer, H, Sudilovsky, D, Lu, Y, and Hylton, N. "MRI phenotype is associated with response to doxorubicin and cyclophosphamide neoadjuvant chemotherapy in stage III breast cancer." Annals of Surgical Oncology 8.6 (2001): 549-559.
PMID
11456056
Source
scival
Published In
Annals of Surgical Oncology
Volume
8
Issue
6
Publish Date
2001
Start Page
549
End Page
559
DOI
10.1245/aso.2001.8.6.549

Reply

Authors
Purves, D; Lotto, B; Polger, T
MLA Citation
Purves, D, Lotto, B, and Polger, T. "Reply." Journal of cognitive neuroscience 12.5 (September 2000): 911-.
PMID
11054932
Source
epmc
Published In
Journal of Cognitive Neuroscience
Volume
12
Issue
5
Publish Date
2000
Start Page
911
DOI
10.1162/jocn.2000.12.5.911a

Current national health insurance coverage policies for breast and ovarian cancer prophylactic surgery

Background: The efficacy of prophylactic mastectomy and oophorectomy in reducing breast and ovarian carcinoma has recently been reported in high-risk women. Because cost has become central to medical decision-making, this study was designed to evaluate currently existing coverage policies for these procedures. Methods: A confidential detailed cross-sectional nationwide survey of 481 medical directors from the American Association of Health Plans, Medicare, and Medicaid was conducted. Results: Of the 150 respondents, 65% (n = 97) had 100,000 or more enrolled members and 35% (n = 53) had fewer than 100,000 enrolled members. Only 44% of private plans have specific policies for coverage of prophylactic mastectomy for a strong family history of breast cancer and 38% of plans for a BRCA mutation. Only 20% of total responding plans had a policy for coverage of prophylactic oophorectomy under any clinical circumstance. Governmental carriers were significantly less likely to have any policy for prophylactic surgery (range, 2%-12%) compared with nongovernmental plans (range, 24%-44%; P < .001). No significant regional differences for coverage policies were identified (P > .05). Conclusions: Significant variations currently exist for health insurance coverage of prophylactic mastectomy and oophorectomy. As genetic testing becomes widespread, more uniform policies should be established to enable appropriate high-risk candidates equal access and coverage for these procedures.

Authors
Kuerer, HM; Hwang, ES; Anthony, JP; Dudley, RA; Crawford, B; Aubry, WM; Esserman, LJ
MLA Citation
Kuerer, HM, Hwang, ES, Anthony, JP, Dudley, RA, Crawford, B, Aubry, WM, and Esserman, LJ. "Current national health insurance coverage policies for breast and ovarian cancer prophylactic surgery." Annals of Surgical Oncology 7.5 (2000): 325-332.
PMID
10864338
Source
scival
Published In
Annals of Surgical Oncology
Volume
7
Issue
5
Publish Date
2000
Start Page
325
End Page
332

Management of ductal carcinoma in situ.

The dramatic increase in the incidence of ductal carcinoma in situ (DCIS) of the breast has made it imperative for all clinicians to develop a better understanding of this disease. Although this preinvasive form of breast cancer is not life-threatening, treatment options may include mastectomy, breast-conserving surgery, radiotherapy, or tamoxifen. Current treatment modalities may be overly aggressive because many cases of DCIS may not recur or progress to invasive cancer. Until we are better able to identify those patients at low risk for progression, it is unlikely that current treatment will change. The adequate understanding of risk assessment is fundamental to the treatment planning for DCIS, and physicians are encouraged to include patients in the decision-making process.

Authors
Hwang, ES; Esserman, LJ
MLA Citation
Hwang, ES, and Esserman, LJ. "Management of ductal carcinoma in situ." The Surgical clinics of North America 79.5 (October 1999): 1007-viii. (Review)
PMID
10572548
Source
epmc
Published In
Surgical Clinics of North America
Volume
79
Issue
5
Publish Date
1999
Start Page
1007
End Page
viii
DOI
10.1016/s0039-6109(05)70058-x

Prophylactic mastectomy in women with a high risk of breast cancer [1] (multiple letters)

Authors
Hamm, RM; Lawler, F; Scheid, D; Ernster, VL; Kuerer, HM; Hwang, ES; Esserman, LJ; Boice, JD; Olsen, JH; Hartmann, LC; Schaid, DJ; Sellers, TA
MLA Citation
Hamm, RM, Lawler, F, Scheid, D, Ernster, VL, Kuerer, HM, Hwang, ES, Esserman, LJ, Boice, JD, Olsen, JH, Hartmann, LC, Schaid, DJ, and Sellers, TA. "Prophylactic mastectomy in women with a high risk of breast cancer [1] (multiple letters)." New England Journal of Medicine 340.23 (1999): 1837-1839.
PMID
10366319
Source
scival
Published In
The New England journal of medicine
Volume
340
Issue
23
Publish Date
1999
Start Page
1837
End Page
1839
DOI
10.1056/NEJM199906103402313

Volume of resection in patients treated with breast conservation for ductal carcinoma in situ

Background: The optimal treatment of ductal carcinoma in situ (DCIS) is one of the most controversial issues in the management of breast cancer. Identification of factors that affect the risk of local recurrence is very important as the incidence of DCIS increases and the use of breast conservation becomes more widespread. Because the extent of resection may affect the relapse rate, we hypothesized that larger volumes of resection (VR) may account for the lower local recurrence rates we have previously found in elderly patients. Methods: Between 1978 and 1990, 173 cases of histologically confirmed DCIS were treated at MSKCC with breast conservation therapy. Of these, complete VR data were available for 126 cases. The VRs thus obtained were divided into two groups, <60 cm3 and ≥60 cm3, and were evaluated for correlating factors. The patients were divided into three groups by age at diagnosis: younger than 40 years, 40 to 69 years, and 70 years or older. Results: The eldest group had a significantly greater proportion of large VRs (30%) as compared to the middle group (11%) and the youngest group (9%) (P = .03, χ2). Although not statistically significant, the large VR group had a lower 6-year actuarial local recurrence rate (5.6%) than did the small VR group (21.3%) (P = .16, log-rank test). This trend was observed even though adjuvant radiotherapy was used less often in patients who had large VRs. Conclusion: Breast conservation surgery for DCIS in elderly patients is more likely to employ a large VR. This may explain, at least in part, the observation that elderly patients have a lower local recurrence rate.

Authors
Hwang, E-S; Samli, B; Tran, KN; Rosen, PP; Borgen, PI; Zee, KJV
MLA Citation
Hwang, E-S, Samli, B, Tran, KN, Rosen, PP, Borgen, PI, and Zee, KJV. "Volume of resection in patients treated with breast conservation for ductal carcinoma in situ." Annals of Surgical Oncology 5.8 (1998): 757-763.
PMID
9869524
Source
scival
Published In
Annals of Surgical Oncology
Volume
5
Issue
8
Publish Date
1998
Start Page
757
End Page
763

Does the proven benefit of mammography extend to breast cancer patients over age 70?

Background. Prospective randomized studies show reduced breast cancer mortality among women offered mammographic screening; yet, few women 70 or older were represented in these trials. We examine the impact of mammography on stage at diagnosis of breast cancer, over the years when mammography came into general use, comparing women aged 40 to 69 with those aged 70 and older. Methods. We reviewed the records of 1,001 consecutive patients 40 and older treated for invasive or in situ breast cancer in the surgical practice of one of us (H.S.C.) between 1979 and 1993, comparing trends in mammography use, means of diagnosis, tumor size, axillary node status, and pathology. Results. The proportion of cases diagnosed by mammography increased over time to a comparable degree in both age groups, as did the proportion of T1 and DCIS or microinvasive cancers. This trend toward earlier stage appears entirely due to an increasing use of mammography. Conclusion. The potential benefit of regular mammography to healthy women aged 70 and older may equal that observed in their younger counterparts.

Authors
Hwang, E-S; III, HSC
MLA Citation
Hwang, E-S, and III, HSC. "Does the proven benefit of mammography extend to breast cancer patients over age 70?." Southern Medical Journal 91.6 (1998): 522-526.
PMID
9634112
Source
scival
Published In
Southern Medical Journal
Volume
91
Issue
6
Publish Date
1998
Start Page
522
End Page
526

Surgical pancreatic complications induced by L-asparaginase

Pancreatitis has been noted to be a potential complication in 2% to 16% of patients undergoing treatment with L-asparaginase for a variety of pediatric neoplasms, but rarely has surgical intervention been necessary. The authors present two fulminant cases of L-asparaginase-induced pancreatitis and review the current literature. The first patient is a 15-year-old boy who underwent induction chemotherapy with L-asparaginase for non-Hodgkin's lymphoma with bone marrow involvement. He presented with diffuse patchy necrosis of the pancreas as well as a large infected pancreatic pseudocyst. He subsequently required operative debridement of the pancreas and external drainage of the pseudocyst. He is currently doing well. The second patient is a 5-year-old boy who was treated with L-asparaginase for a diagnosis of acute lymphocytic leukemia. Within 3 weeks of initiation of therapy, fulminant pancreatitis developed, which progressed to multisystem organ failure. Computed tomography scan demonstrated extensive pancreatic necrosis involving 90% of the gland. He underwent surgical debridement of his necrotic pancreas and wide drainage of the lesser sec. Postoperatively he improved but subsequently multiple complications developed including erosion of his gastroduodenal artery with significant intraabdominal bleeding, which was controlled with angiographic embolization. Subsequently erosion of his endotracheal tube into the innominate vein developed, and he died. L- asparaginase-induced pancreatitis has been described after therapy for various pediatric neoplasms, and the reported cases have usually been self- limiting. However, our cases demonstrate potentially fatal sequelae of this complication and mandate early diagnosis with appropriate surgical intervention in this setting.

Authors
Sadoff, J; Hwang, S; Rosenfeld, D; Ettinger, L; Spigland, N
MLA Citation
Sadoff, J, Hwang, S, Rosenfeld, D, Ettinger, L, and Spigland, N. "Surgical pancreatic complications induced by L-asparaginase." Journal of Pediatric Surgery 32.6 (1997): 860-863.
PMID
9200086
Source
scival
Published In
Journal of Pediatric Surgery
Volume
32
Issue
6
Publish Date
1997
Start Page
860
End Page
863
DOI
10.1016/S0022-3468(97)90636-9

Leiomyosarcoma in childhood and adolescence

Background: Few series of leiomyosarcoma in patients <21 years of age have been reported. We reviewed our institutional experience with this neoplasm to learn disease characteristics, patterns of relapse, and outcome. Methods: The records of 21 patients with leiomyosarcoma admitted to our institution were reviewed retrospectively; 18 of these were diagnosed after 1970. Overall survival was estimated using the Kaplan-Meier method. Results: Ninety-five percent (20 of 21) were initially treated with a wide local excision that was complete with a negative microscopic margin in 10 (48%). There also was a strong correlation between grade and surgical margins. High-grade tumors were associated with a lower rate of complete resection. The majority underwent additional therapy. Radiation was used to treat both initial and recurrent disease in nine patients, with four of these undergoing brachytherapy. Thirteen patients were treated with adjuvant chemotherapy, most commonly doxorubicin (seven patients) and cisplatin (six patients). The median length of survival was 9.3 years, and there were nine disease-related deaths (43%). Of interest was the progressive decrease in survival with time. The 5-year overall survival rate was 79%; the 10-year rate was 49%. Three patients died of progressive disease >10 years after initial diagnosis. Conclusions: We conclude that leiomyosarcomas arising in childhood and adolescence are associated with a good initial chance of survival that decreases progressively over time. Known prognostic factors from larger adult series are consistent with the present data, but they are not provable because of the small number of patients. In particular, the grade was correlated with surgical margins. Published by Lippincott-Raven Publishers © 1997 The Society of Surgical Oncology, Inc.

Authors
Hwang, ES; Gerald, W; Wollner, N; Meyers, P; Quaglia, MPL
MLA Citation
Hwang, ES, Gerald, W, Wollner, N, Meyers, P, and Quaglia, MPL. "Leiomyosarcoma in childhood and adolescence." Annals of Surgical Oncology 4.3 (1997): 223-227.
PMID
9142383
Source
scival
Published In
Annals of Surgical Oncology
Volume
4
Issue
3
Publish Date
1997
Start Page
223
End Page
227

Distribution of the SGLT1 Na+glucose cotransporter and mRNA along the crypt-villus axis of rabbit small intestine

Authors
Hwang, E-S; Hirayama, BA; Wright, EM
MLA Citation
Hwang, E-S, Hirayama, BA, and Wright, EM. "Distribution of the SGLT1 Na+glucose cotransporter and mRNA along the crypt-villus axis of rabbit small intestine." Biochemical and Biophysical Research Communications 181.3 (December 1991): 1208-1217.
Source
crossref
Published In
Biochemical and Biophysical Research Communications
Volume
181
Issue
3
Publish Date
1991
Start Page
1208
End Page
1217
DOI
10.1016/0006-291X(91)92067-T

Characterization of a Na+/glucose cotransporter cloned from rabbit small intestine

Authors
Ikeda, TS; Hwang, E-S; Coady, MJ; Hirayama, BA; Hediger, MA; Wright, EM
MLA Citation
Ikeda, TS, Hwang, E-S, Coady, MJ, Hirayama, BA, Hediger, MA, and Wright, EM. "Characterization of a Na+/glucose cotransporter cloned from rabbit small intestine." The Journal of Membrane Biology 110.1 (August 1989): 87-95.
Source
crossref
Published In
The Journal of Membrane Biology
Volume
110
Issue
1
Publish Date
1989
Start Page
87
End Page
95
DOI
10.1007/BF01870995
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