Titles and Affiliations
Basser Professor in Oncology
Executive Director of the Basser Center for BRCA
Director, MacDonald Cancer Risk Evaluation Center
Abramson Family Cancer Center, Perelman School of Medicine
Member, BCRF Scientific Advisory Board
Research area
Understanding the effect of BRCA mutation on immune function in mutation carriers to optimize and personalize breast cancer treatments.
Impact
Men and women with a BRCA gene mutation have an increased risk of developing ovarian, breast, prostate, and pancreatic cancers. Mutations in BRCA1 and BRCA2 genes in tumors lead to DNA damage, and recent studies have indicated that there may be a link between DNA damage and how the immune system responds to that damage. Dr. Domchek and her team are seeking to understand more about normal immune responses in individuals with mutations in BRCA1 and BRCA2 genes. This knowledge is needed to determine the effect on tumor surveillance, potential response to future cancer prevention vaccines, and individual response to immunotherapies.
Progress Thus Far
Dr. Domchek has focused her research efforts on understanding the differences in the immune system of people with inherited BRCA mutations compared to those who do not carry mutations. In one part of their study, Dr. Domchek and her team looked at how their immune systems responded to a flu vaccine. While most immune responses were similar, they did find one important difference: those with BRCA mutations had a specific type of B cell, or an immune cell that makes infection-fighting antibodies, that may not be functioning normally. This could point to a weakness in how the immune system of BRCA mutation carriers adapts to threats.
In the second part of their study, they examined both healthy and tumor breast tissue to better understand how the tumor microenvironment differs in those with BRCA-related triple-negative breast cancer (TNBC). By studying local immune patterns, they can identify early warning signs and uncover new opportunities for treatment. They saw more signs of DNA damage in key immune cells and shifts in immune cell types that could suggest early signs of immune system fatigue.
What’s next
In the next phase of their work, Dr. Domchek and her team will take a deeper look at the immune system by analyzing additional blood and breast tissue samples from people with and without BRCA mutations. They plan to isolate and study B cells to better understand how they respond to vaccines. They will also examine healthy breast tissue from individuals with BRCA mutations to look for very early changes in cells and immune activity that might signal future cancer risk. By using advanced tools that allow them to study individual cells in great detail, they hope to uncover early warning signs and new opportunities to prevent breast cancer before it starts.
Biography
Susan M. Domchek, MD is the Basser Professor in Oncology at the Perelman School of Medicine of the University of Pennsylvania. She serves as Executive Director of the Basser Center for BRCA at the Abramson Cancer Center and Director of the MacDonald Cancer Risk Evaluation Program. Her work focuses on clinical applications of genetic susceptibility to cancer, including risk assessment, screening, prevention, and treatment. Dr. Domchek is particularly interested in developing new cancer therapies, such as PARP inhibitors in BRCA associated breast cancer. She is the Chair of the Translational Advisory Committee on the OlympiA study of adjuvant Olaparib (LYNPARZA®, PARP inhibitor) in high risk BRCA1/2 associated breast cancer.
An elected member of the National Academy of Medicine, the American Society of Clinical Investigation, the Association of American Physicians, and a Fellow of the American Association for Cancer Research. Dr. Domchek is also a member of the American Society of Clinical Oncology for which she had served on several committees. A significant contributor to the oncology literature, she has authored/co-authored more than 350 articles appearing in scholarly journals including the New England Journal of Medicine, the Journal of the American Medical Association and the Journal of Clinical Oncology. Dr. Domchek serves on several editorial boards and on the Scientific Advisory Board for the Breast Cancer Research Foundation.
