Jennifer Plichta

PURPOSE: Given the heterogeneity and improvement in outcomes for metastatic breast cancer (MBC), we developed a staging system that refines prognostic estimates for patients with metastatic cancer at the time of initial diagnosis, de novo MBC (dnMBC), on the basis of survival outcomes and disease-related variables. METHODS: Patients with dnMBC (2010-2016) were selected from the National Cancer Database (NCDB). Recursive partitioning analysis (RPA) was used to group patients with similar overall survival (OS) on the basis of clinical T category, grade, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2, histology, organ system site of metastases (bone-only, brain-only, visceral), and number of organ systems involved. Three-year OS rates were used to assign a final stage: IVA: >70%, IVB: 50%-70%, IVC: 25 to <50%, and IVD: <25%. Bootstrapping was applied with 1,000 iterations, and final stage assignments were made based on the most commonly occurring assignment. Unadjusted OS was estimated. Validation analyses were conducted using SEER and NCDB. RESULTS: At a median follow-up of 52.9 months, the median OS of the original cohort (N = 42,467) was 35.4 months (95% CI, 34.8 to 35.9). RPA stratified patients into 53 groups with 3-year OS rates ranging from 73.5% to 5.7%; these groups were amalgamated into four stage groups: 3-year OS, A = 73.2%, B = 61.9%, C = 40.1%, and D = 17% (log-rank P < .001). After bootstrapping, the survival outcomes for the four stages remained significantly different (log-rank P < .001). This staging system was then validated using SEER data (N = 20,469) and a separate cohort from the NCDB (N = 7,645) (both log-rank P < .001). CONCLUSION: Our findings regarding the heterogeneity in outcomes for patients with dnMBC could guide future revisions of the current American Joint Committee on Cancer staging guidelines for patients with newly diagnosed stage IV disease. Our findings should be independently confirmed.

OBJECTIVES: To characterize and quantify accumulating immunological alterations, pre- and post-operatively in patients undergoing elective surgical procedures. SUMMARY BACKGROUND DATA: Elective surgery is an anticipatable, controlled human injury. Although the human response to injury is generally stereotyped, individual variability exists. This makes surgical outcomes less predictable, even after standardized procedures, and may provoke complications in patients unable to compensate for their injury. One potential source of variation is found in immune cell maturation, with phenotypic changes dependent on an individual's unique, lifelong response to environmental antigens. METHODS: We enrolled 248 patients in a prospective trial facilitating comprehensive biospecimen and clinical data collection in patients scheduled to undergo elective surgery. Peripheral blood was collected pre-operatively, and immediately upon return to the post- anesthesia care unit. Postoperative complications that occurred within 30 days after surgery were captured. RESULTS: As this was an elective surgical cohort, outcomes were generally favorable. With a median follow-up of 6 months, the overall survival at 30 days was 100%. However, 20.5% of the cohort experienced a postoperative complication (infection, readmission, or system dysfunction). We identified substantial heterogeneity of immune senescence and terminal differentiation phenotypes in surgical patients. More importantly, phenotypes indicating increased T-cell maturation and senescence were associated with postoperative complications and were evident pre-operatively. CONCLUSIONS: The baseline immune repertoire may define an immune signature of resilience to surgical injury and help predict risk for surgical complications.

BACKGROUND: Initial trials evaluating Oncotype DX, reported as a recurrence score (RS) from 0 to 100, were not powered to evaluate overall survival, and premenopausal women were underrepresented. The purpose of this study was to explore the benefit of chemotherapy according to RS among younger women eligible for oncotype testing. METHODS: Women aged 40-50, diagnosed with HR-positive, HER2-negative breast cancer between 2010 and 2017 were selected from the National Cancer Database (NCBD). Patients were grouped by age, RS, nodal status, and chemotherapy receipt. Kaplan-Meier curves were used to compare unadjusted overall survival (OS) between the groups, and log-rank tests were used to test for a difference between groups. Cox proportional hazards models were used to examine the association between select factors and OS. RESULTS: A total of 15,422 patients met inclusion criteria, 45.3% of whom received chemotherapy. Median follow-up time was 66.4 (50.6-86.6) months. Patients who received chemotherapy were more likely to have higher-stage and higher-grade tumors, tumors that were PR-negative, and have higher RS (p < 0.001 for all). RS was prognostic for OS regardless of nodal status. After adjustment, chemotherapy was associated with a significant improvement in OS only in the pN1 RS 31-50 subgroup (p = 0.02). CONCLUSIONS: RS retains its prognostic value in younger patients with early stage HR-positive, HER2-negative breast cancer. Chemotherapy survival benefit was limited to patients aged 40-50 with pN1 disease and RS of 31-50. Therefore, chemotherapy decision-making should be especially preference-sensitive in women aged 40-50 with intermediate RS, where it may not provide a survival benefit for many women.

Identifying factors associated with persistent pain after breast cancer surgery may facilitate risk stratification and individualised management. Single-population studies have limited generalisability as socio-economic and genetic factors contribute to persistent pain development. Therefore, this prospective multicentre cohort study aimed to develop a predictive model from a sample of Asian and American women. We enrolled women undergoing elective breast cancer surgery at KK Women's and Children's Hospital and Duke University Medical Center. Pre-operative patient and clinical characteristics and EQ-5D-3L health status were recorded. Pain catastrophising scale; central sensitisation inventory; coping strategies questionnaire-revised; brief symptom inventory-18; perceived stress scale; mechanical temporal summation; and pressure-pain threshold assessments were performed. Persistent pain was defined as pain score ≥ 3 or pain affecting activities of daily living 4 months after surgery. Univariate associations were generated using generalised estimating equations. Enrolment site was forced into the multivariable model, and risk factors with p < 0.2 in univariate analyses were considered for backwards selection. Of 210 patients, 135 (64.3%) developed persistent pain. The multivariable model attained AUC = 0.807, with five independent associations: age (OR 0.85 95%CI 0.74-0.98 per 5 years); diabetes (OR 4.68, 95%CI 1.03-21.22); pre-operative pain score at sites other than the breast (OR 1.48, 95%CI 1.11-1.96); previous mastitis (OR 4.90, 95%CI 1.31-18.34); and perceived stress scale (OR 1.35, 95%CI 1.01-1.80 per 5 points), after adjusting for: enrolment site; pre-operative pain score at the breast; pre-operative overall pain score at rest; postoperative non-steroidal anti-inflammatory drug use; and pain catastrophising scale. Future research should validate this model and evaluate pre-emptive interventions to reduce persistent pain risk.