MBC PROJECT OVERVIEW and Q & A with TERRY HYSLOP, PHD

Susan G. Komen and Gilead Sciences, Inc. MBC Collaborative Research Grant

Co-Principal Investigators

Terry Hyslop, PhD
Duke University School of Medicine, Duke Cancer Institute
Professor, Department of Biostatistics & Bioinformatics

Melissa Troester, PhD
UNC Gillings School of Global Public Health, UNC Lineberger Comprehensive Cancer Center
Professor, Department of Epidemiology
Research Professor, Department of Pathology and Laboratory Medicine
Director, UNC Center for Environmental Health and Susceptibility

PROJECT SUMMARY

This project will leverage high quality, individual-level tumor biology and social determinants of health data from the Carolina Breast Cancer Study (CBCS) with community-level variables in order to better understand disparities. Researchers will evaluate how stress contributes to higher metastasis rates and worse breast cancer outcomes in Black women as compared to white women. This evidence-based research will support interventions to improve breast cancer outcomes for Black women.

Q & A with Terry Hyslop, PhD

In what ways will this grant build on/advance your current research? Or is this brand-new research?

TH: I have been researching disparities in cancer, and in particular, breast cancer, for a number of years. One of my earliest funded projects as a PI came from Susan G. Komen (foundation) to assess how to use neighborhood-level measures of socio-economic status and its impact on breast cancer disparities.

What is new about this project, is that we will focus on metastatic breast cancer, that is, how social stressors may contribute to disparities in risk for developing metastatic breast cancer, and how these stressors may contribute to disparities in risk for already having metastatic breast cancer when diagnosed with breast cancer.

Through this partnership with UNC, we will have access to both the Carolina Breast Cancer Study (CBCS) cohort, a large longitudinal cohort of breast cancer patients in North Carolina, but also the expertise of Melissa Troester, PhD (and her team) who is both my co-PI on the Susan G. Komen MBC project AND the PI of the Carolina Breast Cancer Study (CBCS).

What are the next steps for this research project?

TH: My students and I and the UNC team have been meeting for about a year, sharing ideas and techniques, and we are now putting in place the protocols required for data sharing across the institutions. A unique feature of the CBCS cohort, is that we will have access to de-identified breast cancer clinical information, patient surveys, panels of immune markers and high-dimensional gene expression data from patients across 40 counties from North Carolina, representing both urban and rural areas of the state and a broad range of socio-economic environments.

What are the end goals of the grant?

TH: Our end goal is to develop a rigorous statistical modeling framework that will allow us to integrate the broad range and volumes of data to improve our understanding of contributors to metastatic breast cancer disparities.

In particular, we want to further our knowledge of the relationship of social stressors and immune system signaling. There is a significant amount of research focusing on using immune therapies in cancer, and furthering our understanding of those at risk for non-response to these therapies (patients for whom these therapies don’t work, also called immunotherapy resistance) can guide clinical trial recruitment as well as alternative treatment strategies for these patients.

Will there be any clinical trials as part of the three-year project plan?

TH: We do not plan any clinical trials as part of this project, but we anticipate that results from our study will be useful in identifying characteristics of sub-populations that would potentially benefit from either behavioral/lifestyle interventions and/or treatment trials targeted at improving breast cancer outcomes, particularly for metastatic patients.

Who else, in addition to you and Dr. Troester is on the research project team?

TH: As we consider the important social constructs in this work, we are partnering with Tomi Akinyemiju, PhD, DCI Associate Director for Community Outreach, Engagement and Equity, who focuses on the impact of stress on triple negative breast cancer in Black women in Nigeria. We have also been working with Dr. Akinyemiku on the investigation of neighborhood-level structural measures of racism. She is a co-investigator on our project.

We have several patient advocates aiding us in our research. Patty Spears will serve as the Lead Advocate for our project. Patty is a 20-year breast cancer survivor and a scientific research manager and patient advocacy expert at UNC Lineberger Comprehensive Cancer Center.

We will also be working with Melissa Van Lokeren, who is living with metastatic breast cancer. Melissa is an advocate for the UNC Breast Specialized Program of Research Excellence and is on the leadership team of the UNC Patients and Researchers Together (PART) initiative to increase awareness and donations of biospecimens for cancer research at UNC Lineberger. 

Additionally, we are joined by Marian Johnson-Thompson, PhD, who is a professor emerita of Biology at the University of the District of Columbia and an adjunct professor in the UNC-Chapel Hill School of Public Health. Marian is a Black breast cancer advocate and a health disparities expert and is a former Steering Committee member of Komen Advocates in Science, and a Komen Scholar. Marian has been vice-chair of the NC Department of Environmental Quality Secretary’s Environmental Justice and Equity Advisory Board since 2018. 

This grant will also enable me to hire a post-doctoral researcher, who will join us in the development of the novel statistical modeling approaches.

MBC RESEARCH PROJECT OVERVIEW and Q & A with JENNIFER FREEDMAN, PHD

Susan G. Komen and Blue Cross NC MBC Disparities Collaborative Research Grant

Co-Principal Investigators

Jennifer Freedman, PhD
Duke Cancer Institute, Duke University School of Medicine
Associate Professor, Department of Medicine
Co-Director, Patierno/Freedman/George Lab for Cancer Research

Steven Patierno, PhD
Duke Cancer Institute, Duke University School of Medicine
Deputy Director, Duke Cancer Institute
Co-Director, Patierno/Freedman/George Lab for Cancer Research
Professor, Department of Medicine
Professor, Department of Pharmacology and Cancer Biology
Professor, Department of Family Medicine and Community Health
Core Faculty Member, Duke-Margolis Center for Health Policy

Katherine Hoadley, PhD
University of North Carolina Lineberger Comprehensive Cancer Center
Director, Hoadley Lab (biology of cancer through gene expression analyses and integrative genomic approaches)
Assistant Professor, Genetics, Computational Medicine Program
UNC-Chapel Hill Cancer Genetics

PROJECT SUMMARY

This project will identify differences in RNA splicing and differences in immune system characteristics between metastatic breast cancer patients of African versus European ancestry. The team hopes to determine if and how these differences impact the growth and spread of breast cancer. Due to significant disparities in breast cancer outcomes for Black women,;a greater understanding of the role that these underlying biological mechanisms play in breast cancer metastasis is essential to the development of better treatments and improved outcomes.

Q & A with Jennifer Freedman, PhD

In what ways will this grant build on/advance your current research? Or is this brand-new research?

JF: Recently, we have identified in our lab, differences in RNA splicing by ancestry in a number of cancers exhibiting disparities among racial groups, including primary breast cancer, which is breast cancer that has not spread to other locations in the body.

Dr. Patierno and I will be partnering with Dr. Katherine Hoadley, who directs the Hoadley Lab at UNC Lineberger Comprehensive Cancer Center.

The Hoadley Lab has recently identified differences in immune system characteristics  (immune expression signatures and immune cell composition) in primary breast cancer and between Black patients and white patients.

This grant will build on/advance our lab research and the Hoadley Lab’s research beyond primary breast cancer — to metastatic breast cancer. The next step for our joint research will be to determine if these differences (in RNA splicing and in immune system characteristics in metastatic breast cancer patients of African versus European ancestry) are causing breast cancer cells to grow and spread more quickly in Black women with African ancestry.

What are the end goals of the grant?

JF: The end goals of the grant are to take a first step toward developing new personalized drugs for metastatic breast cancer by identifying new targets these drugs can be developed against. The work will also significantly increase the number of biologically characterized metastatic breast cancers from patients of African ancestry, which will be available to all scientists for study. Ultimately, the work will improve outcomes for Black women with metastatic breast cancer as well as for women of all races and ethnicities with breast cancer that grows and spreads more quickly.

Who are your other collaborators on the project research team?

JF: From Duke, our research collaborators include co-investigators Carey Anders, MD (breast medical oncologist; medical director, Duke Center for Brain and Spine Metastasis at DCI; interim chief of the Department of Medicine’s Division of Medical Oncology) and Kouros Owzar, PhD (director, DCI Bioinformatics Shared Resource); as well as Tyler Allen, PhD, postdoctoral associate in our lab (Patierno/Freedman/George Lab for Cancer Research); bioinformaticians Alexander Sibley, and Jeremy Gresham; and Amanda Van Swearingen, PhD, senior research associate with the Duke Brain and Spine Metastasis Center at DCI.

From UNC, research collaborators include co-investigators Lisa Carey, MD, FASCO (breast medical oncologist and deputy director of Clinical Sciences, Lineberger Comprehensive Cancer Center) and Naim Rashid, PhD (associate professor, Department of Biostatistics, and  research associate professor, UNC Lineberger Comprehensive Cancer Center)

We will also be working closely with two individuals who bring their knowledge and skills and their unique and valuable perspectives as metastatic breast cancer patients and patient advocates —— to our project.

Katrina Cooke, BA, is a metastatic breast cancer patient advocate and mother of two boys who has been living with metastatic breast cancer since being diagnosed at DCI in 2011 at the age of 36. She’s a professional speaker, peer mentor, peer group facilitator and advocate. Building on her bachelor’s degree in psychology, she underwent training with the American Cancer Society to become a peer mentor and training with SHARE Cancer Support to become a peer group facilitator. Since 2017, she has been a patient advocate and metastatic breast cancer group facilitator with Komen North Carolina Triangle to the Coast as well as a member of the Duke Cancer Institute Oncology Patient and Family Advisory Council (OPAC). Since 2018, she has served as community co-chair of OPAC and she also sits on OPAC’s chemo-immunotherapy education committee. Since January of 2020, she has been a member of the Duke University Health System Patient and Family Advisory Council (PFAC).

“I have had the pleasure of being a part of many Quality Improvement projects and research studies as a patient advisor and team member.  I am excited to partner with researchers at Duke and UNC as they come together to get us closer to making sure metastatic breast cancer is not the death sentence that it is now. I am confident that when patients and researchers come together as one that the needle will begin to move on metastatic breast cancer and make a life and death difference in the lives of those like me… By being a part of this groundbreaking research I will be able to provide input and insight as an actual metastatic breast cancer patient on the design, conduct, analysis, and dissemination of the findings.”  — Katrina Cooke

Amelia Stanley is a metastatic breast cancer patient advocate who was diagnosed nearly two years ago at the age of 34 with breast cancermetastasis to the bone. Her family has a long history of breast and gynecological cancers. She has been treated at UNC Lineberger Comprehensive Cancer Centerince January 2020 and has shown a remarkable response to treatment. This project will be her first foray into patient advocacy.

Katrina Cooke and Amelia Stanley provided their insight and input throughout the project design and grant application process and they will be involved in the project’s implementation and the analysis and dissemination of the project’s findings. During the grant application preparation process, they enjoyed discussing the design of the project and reviewing the lay abstract of the application to ensure that the language and the impact would be clear to metastatic breast cancer patients like them. They were in regular communication with the team, by email or phone and attended biweekly team meetings.

Throughout the duration of this project, they will be attending events that the team is involved in with that include additional scientists and/or community stakeholders, including biweekly internal seminars, an annual external scientific conference, and monthly community events, such as the Duke Cancer Institute’s Office of Health Equity Conversations with Our Community. For such events, they will be preparing project materials with the team and co-presenting. These opportunities will enhance their knowledge and skills related not only to our specific research project, but to metastatic breast cancer research in general. And they will help connect our project researchers with community stakeholders as well as other patients and advocates in our local Susan G. Komen affiliate.

MBC RESEARCH PROJECT OVERVIEW and Q & A with ZACHARY HARTMAN, PHD

Susan G. Komen Metastatic Breast Cancer Collaborative Research Grant

Co-Principal Investigators

Zachary Hartman, PhD
Duke Cancer Institute, Duke University School of Medicine
Director, Center for Applied Therapeutics, Duke Surgery
Director, Tumor Immunology and Immunotherapeutics Laboratory (The Hartman Lab)
Associate Professor, Department of Surgery
Associate Professor, Department of Pathology

Benjamin Vincent, MD
UNC Lineberger Comprehensive Cancer Center, UNC-Chapel Hill
Principal Investigator, Vincent Lab (cancer immunology, immunobiology and immunogenomics)
Assistant Professor and joint faculty member, Department of Microbiology and Immunology 

PROJECT SUMMARY

The team will develop a personalized anti-tumor vaccine for patients with advanced Triple Negative Breast Cancer that will mobilize the body’s immune system (primarily T-cells and perhaps other immune cells) to shut down tumor growth and metastasis.

Q & A with Zachary Hartman, PhD

In what ways will this grant build on/advance your current research? What are the next steps?

ZH:Our team has previously done work on thisin situvaccine strategy and have a paper currently in review with the Journal for ImmunoTherapy of Cancer (JITC),which describes this strategy in colorectal cancer. We believe it may actually work even better in breast cancer.

This grant will enable us to test an innovative new strategy to stimulate ‘personalized’ immunity against a patient’s metastatic breast cancer, in the hopes of provoking specific anti-tumor immune responses (T-cell responses) against distant metastases.

Dr. Vincent will be working with us to test this immunotherapy in mice with triple negative breast cancer to determine if we can stimulate and elicit ‘personalized’ anti-tumor immunity against metastatic breast cancer. We are especially excited about the translational potential of this project, as an ”off-the-shelf” therapy that could even be paired with other immunotherapies that have shown some potential in breast cancer, such as immune checkpoint inhbition.

The next step will be to test this optimized strategy in Phase I proof-of-concept clinical trials at Duke and UNC in conjunction with biotech company *Replicate Bioscience, Inc., the maker of the vaccine tested in our proposal. This collaboration will be essential to moving into the next phase of research — clinical trials.

Who are your other collaborators on the project?

ZH:Our team also includes multiple advocates and collaborators who are essential for our team.

These patient advocates will be an active part of our team and will meet with us on a regular basis to see data and provide feedback. In the long term, they’ll be instrumental to patient engagement and advocacy in support of the Phase I clinical trial.

The patient advocates include:

Melissa Van Lokeren, who is living with metastatic breast cancer, is an advocate for the UNC Breast Specialized Program of Research Excellence and is on the leadership team of the UNC Patients and Researchers Together (PART) initiative to increase awareness and donations of biospecimens for cancer research at UNC Lineberger.

Katherine (Katie) Mackin, PA, MHSc, is a cancer research advocate who is living with metastatic breast cancer. Katie was diagnosed in January 2018 at age 34 with stage 4 (metastatic) breast cancer when her son was just eight months old. She underwent targeted treatment, radiation, chemotherapy, and reconstructive spine surgery to avoid becoming paralyzed. Katie works full time as a physician assistant at an orthopaedics clinic and has been actively involved in breast cancer research advocacy since 2020 through her work with Duke Cancer Institute (DCI) and the Duke Brain and Spine Metastasis Center at DCI. Prior to her metastatic breast cancer diagnosis, she trained and worked as a physician assistant, as an emergency medical technician, and as a research associate in a lab at Duke.

“These life experiences have provided me with the knowledge to both understand the medicine and the science behind the proposed research, as well as appreciate what is truly important to metastatic patients to ensure this is not lost in the process of conducting such intricate research. Recent collaboration with breast cancer researchers has enabled me to share my perspective as they develop grant applications.” – Katie Mackin

Rhonda Howell is an active advocate for patients and cancer research who’s been living with stage 4 metastatic breast cancer (and in active treatment at DCI) for about six years. She was originally diagnosed with stage 2 breast cancer at age 34. After a double mastectomy, four rounds of chemotherapy, 35 radiation treatments and taking daily tamoxifen, she was declared cancer free. However, two years later, in 2015, she was diagnosed with stage 4 (metastatic) breast cancer, with metastases to her liver and bones. She was 36 years old at the time and her son was three. Rhonda recently celebrated her 42nd birthday. She has raised thousands in research funds, including for Komen.

*Zachary Hartman, PhD, with Duke professor Herbert Kim Lyerly, MD, are co-founders and scientific advisors with this Duke spinout

LEARN MORE: MBC Collaborative Research Initiative

Susan G. Komen Metastatic Breast Cancer Collaborative Research Initiative Overview 

WATCH: Celebrating the launch of the MBC Collaborative Research Initiative with exec. director of Duke Cancer Institute Michael Kastan, MD, PhD, and director of UNC Lineberger Comprehensive Cancer Center Shelley Earp, MD

WATCH: Metastatic Breast Cancer Collaborative Research Initiative Grant Award Ceremony (10.13.21)

Duke, UNC teams getting $1.5 million for breast cancer research will study vaccines, death rates in Black women (WRAL TV)