Titles and Affiliations
Chief of Breast Oncologic Pathology,
Dana-Farber/Brigham and Women’s Cancer Center
Professor of Pathology, Harvard Medical School
Associate Director, Breast Oncology Program
Research area
Understanding the molecular nature of treatment response and resistance in breast cancer.
Impact
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.
Progress Thus Far
Using tumor samples from the INFORM trial, the research team applied artificial intelligence to analyze tumor characteristics before treatment. They have found that among tumors with low levels of immune cell activity, those with more uniform immune cells responded significantly better to chemotherapy. In fact, these tumors responded as well as those with high levels of immune activity, offering a new way to identify patients who may benefit from treatment even when traditional indicators suggest otherwise. In parallel, the team analyzed genetic material from the tumors and blood samples. Tumors that had acquired more mutations were found to be more resistant to chemotherapy, while two blood-based markers were associated with improved response to the chemotherapy drug cisplatin.
What’s next
In the upcoming year, Drs. Tung and Schnitt will further compare tumor tissue before and after chemotherapy to identify changes that allow some cancer cells to survive. This is especially important for women with inherited BRCA1 or BRCA2 mutations, since these mutations usually make tumors more sensitive to chemotherapy. However, sometimes the tumor can acquire additional genetic changes that restore the function of the BRCA gene, essentially masking the inherited mutation in the cancer cells. This makes it more challenging to treat, since it may become resistant to PARP inhibitors, a type of drug often used in patients with BRCA mutations. Learning how tumors develop this type of resistance could guide better treatment decisions in the future.
Biography
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.
