Beth Israel Deaconess Medical Center Boston, Massachusetts
Director, Cancer Risk and Prevention Program Beth Israel Deaconess Medical Center Professor of Medicine, Harvard Medical School
Understanding the molecular nature of treatment response and resistance in breast cancer.
The BRCA1 and BRCA2 genes are the most affected genes in hereditary breast and ovarian cancers. Normally, BRCA1 and BRCA2 function to ensure the proper repair of DNA damage, but mutations in these genes lead to rapid accumulation of DNA errors, which leads to cancer. However, this defect also makes BRCA-mutated cells vulnerable to treatments that cause DNA damage. Cisplatin, a platinum-containing chemotherapy agent not typically used to treat breast cancer, has demonstrated good activity in BRCA mutation carriers with breast cancer and in some women with triple-negative breast cancer (TNBC). Recently, Drs. Tung and Schnitt completed the INFORM trial, which showed that while cisplatin is an active agent in BRCA mutation carriers with breast cancer, it was not more effective than the standard chemotherapy regimen. Drs. Tung and Schnitt are evaluating why some breast cancers respond to chemotherapy, including platinum chemotherapy, and other breast cancers do not.
Drs. Tung and Schnitt have conducted extensive molecular analysis of tumor tissue and blood from 92 BRCA mutation carriers enrolled in INFORM, representing the largest study that evaluates pre-surgical chemotherapy in BRCA mutation carriers. They have found that tumors that were stimulated an immune response, characterized by the infiltration of immune cells, responded better to chemotherapy. The team found that features in the tissue immediately surrounding the tumor, known as the tumor microenvironment, predicted response to chemotherapy.
In the upcoming year, Drs. Tung and Schnitt will validate their findings using tumor tissue from another trial. They will continue their analysis of the tumor microenvironments and tumor genomic data to identify clues about how cancer responds to chemotherapy. While this work is being conducted in BRCA-driven breast cancers, the results will inform the behavior of non-BRCA-driven breast cancers.
Nadine Tung, MD is the Director of the Cancer Genetics and Prevention Program at Beth Israel Deaconess Medical Center (BIDMC), which she established in 1997 to evaluate patients and families with hereditary cancer syndromes. She is also a breast medical oncologist and a member of the Dana-Farber Harvard Cancer Center as well as Professor of Medicine at Harvard Medical School. She graduated from Princeton University in 1980 and Harvard Medical School in 1984. Dr. Tung’s research focuses on hereditary causes of breast cancer as well as effective strategies for breast cancer prevention and treatment. Much of her research has focused on women with BRCA1 and BRCA2 mutations, studying the genetic and environmental factors that influence cancer development as well as the biology and prognosis of the breast cancers they develop. Dr. Tung was recently elected as a Fellow of the American Society of Clinical Oncology (ASCO).
2007
Dana-Farber Cancer Institute/Brigham and Women’s Cancer Center Boston, Massachusetts
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