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Christine B. Ambrosone, PhD
Professor and Chair
Department of Cancer Prevention and Control
Roswell Park Cancer Institute
Buffalo, New York
- Seeking answers to why some women develop aggressive breast cancers called triple negative.
- Studies are ongoing to understand the racial disparities in triple negative breast cancer incidence and outcome.
- These studies are advancing our understanding of disparities in breast cancer outcome and will provide a framework for future studies.
Triple negative breast cancer (TNBC) is an aggressive disease that disproportionately affects women of African ancestry. Understanding the biological factors that underlie this disparity will enable the development of better treatments and prevention strategies. Drs. Ambrosone and Hong have identified several factors including breast feeding and host immune factors that may influence the incidence of TNBC in black women.
Full Research Summary
Triple negative breast cancer (TNBC) is an aggressive disease. While it accounts for less than 20 percent of breast cancer diagnosed in the U.S., women of African American descent are two times more likely to be diagnosed with TNBC than white women.
Drs. Ambrosone and Hong are interested in understanding the underlying biology of this disparity. In ongoing studies, they have shown that levels of a gene called FOXA1 that is important in preventing development of ER-negative tumor were lower in ER-negative breast cancers in women who did breastfeed after childbirth. To determine if this pattern of FOXA1 expression reflects reproductive events prior to development of cancer, the research team will compare FOXA1 levels in breast cancer patients and in women without cancer.
In other work Drs. Ambrosone and Hong are studying how the immune system may influence the risk of TNBC. In the past year, they showed that there are differences in circulating levels of some immune factors and in genes that regulate immune response according to breast cancer subtypes. These differences were also seen between American women of European (EA) and African (AA) ancestry.
High levels of immune cells called tumor infiltrating lymphocytes (TILs) in TNBC is usually a sign of better prognosis. In spite of this trend, the researchers noted higher TILs but worse prognosis in TNBC tumors from AA women compared to white women. When they looked deeper in the tumors from black women they found that the majority of TILs were dysfunctional and thus not effective in tumor cell killing.
In the coming year, they will examine types of immune cells in relation to survival, which may inform more effective immunotherapies for women with aggressive breast cancer.
Identifying immune subsets and ratios that differ by race and subtypes will be crucial for future studies of the role of immune factors in disparities in treatment outcomes and may provide critical information for future studies of immunotherapy, particularly for women with ER negative breast cancer.
Dr. Ambrosone is a Professor of Oncology and Chair of the Department of Cancer Prevention and Control at Roswell Park Cancer Institute. She is also co-leader of the CCSG Population Sciences Program. She was formerly a member of NCI’s EPIC Study Section and the ACS’s study section on Carcinogenesis, Nutrition and the Environment, and has served on several special emphasis panels and SPORE reviews. She is former Senior Editor for Cancer Research, was a member of the Board of Scientific Advisors to the Director of the National Cancer Institute until 2012, and served on the Interagency Breast Cancer and Environmental Research Coordinating Committee, established by the US Secretary of Health and Human Services to examine the state of the science on breast cancer and the environment and provide recommendations for future directions in research.
Dr. Ambrosone’s research focuses on both the etiology of breast cancer and factors that influence recurrence and survival after breast cancer diagnosis. She is principal investigator with colleagues at Boston University and University of North Carolina of a multi-center study to identify genetic and non-genetic factors that could account for the high prevalence of more aggressive breast tumors among African-American women. She is also involved in studies of genetic variability in cancer treatment outcomes (pharmacogenetics) and the potential effects of diet, supplements and lifestyle factors during and after therapy on breast cancer treatment outcomes.