Dana-Farber Cancer Institute/Brigham and Women’s Cancer Center Boston, Massachusetts
Chief of Breast Oncologic Pathology, Dana-Farber/Brigham and Women’s Cancer Center Professor of Pathology, Harvard Medical School Associate Director, Breast Oncology Program
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. Schnitt and Tung 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. Schnitt and Tung 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.
Stuart Schnitt, MD is the Chief of Breast Oncologic Pathology for the Dana-Farber/Brigham and Women’s Cancer Center, Associate Director of the Dana-Farber Cancer Institute/Brigham and Women’s Hospital Breast Oncology Program, Senior Pathologist at Brigham and Women’s Hospital, Professor of Pathology at Harvard Medical School and an internationally recognized expert in breast pathology. Dr. Schnitt completed his internship and residency in Anatomic and Clinical Pathology at Beth Israel Hospital in Boston followed by a fellowship in surgical pathology, also at Beth Israel Hospital. He was a faculty member in the Department of Pathology at Beth Israel Hospital/Beth Israel Deaconess Medical Center from 1984 to 2017, including 11 years as Director of Anatomic Pathology and subsequently Vice Chair for Anatomic Pathology. He has published over 350 original research and review articles, editorials, commentaries, and book chapters, primarily in breast diseases. Dr. Schnitt is a Past President of the United States and Canadian Academy of Pathology (2010-2011) and has many other notable honors. He has lectured extensively around the world, and his research interests and contributions to our understanding of benign breast disease and cancer have been broad but have largely focused on risk factors for local recurrence in patients with invasive breast cancer and ductal carcinoma in situ treated with breast conserving therapy, benign breast disease and breast cancer risk, and stromal-epithelial interactions in breast tumor progression.
2007
Beth Israel Deaconess Medical Center Boston, Massachusetts
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