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Stuart J. Schnitt, MD
Chief of Breast Oncologic Pathology,
Dana Farber/Brigham and Women’s Cancer Center
Associate Director, Breast Oncology Program,
Dana-Farber Cancer Institute/ Brigham and Women’s Hospital
Professor of Pathology, Harvard Medical School
Goal: To determine which patients with early-stage, BRCA-driven breast respond best to chemotherapy.
Impact: Drs. Schnitt and Tung completed a clinical trial that compares the effectiveness of standard chemotherapy to the chemotherapy drug cisplatin in early-stage breast cancer patients who have inherited mutations in the BRCA1 and BRCA2 genes. Their findings could help identify which patients will benefit from cisplatin, which is typically not used to treat breast cancer.
What’s next: Having completed the trial, Drs. Schnitt and Tung are now analyzing samples from the patients enrolled in the study to look for biomarkers that predict which patients respond best to each therapy.
Normally, BRCA genes produce proteins that help repair DNA damage. But this function is impaired in individuals who have mutations in these genes, which leads to breast and other forms of cancer. However, this makes BRCA-mutated cells vulnerable to treatments that cause DNA damage. Research suggests that the chemotherapy drug cisplatin may be effective in treating patients with BRCA-driven breast cancers because it causes a type of DNA damage that BRCA-deficient cells can’t repair. Drs. Schnitt and Tung aim to determine if biomarkers can predict whether cisplatin or standard chemotherapy would be better to treat BRCA carriers with newly diagnosed breast cancer.
Full Research Summary
Research area: Determining the best treatment options for patients with inherited BRCA mutations and newly diagnosed breast cancer.
Impact: Drs. Schnitt and Tung recently completed a randomized clinical trial that showed that cisplatin and standard chemotherapy agents (i.e. doxorubicin and cyclophosphamide, AC) are both effective in women with early-stage breast cancer with inherited BRCA1/2 mutations. Analyses of specimens collected could uncover valuable markers of treatment response that
may inform difficult treatment decisions for breast cancer patients with inherited BRCA1/2 mutations.
Current investigation: Drs. Schnitt and Tung are working with Dr. Judy Garber—and teams from Boston and medical institutions across the country through the Translational Breast Cancer Research Consortium (TBCRC)—to collect and analyze samples from a rare group of breast cancer patients. Blood and tumor specimens from BRCA mutation carriers will be analyzed to identify markers that distinguish those who do better on cisplatin, when compared with standard chemotherapy treatment.
What they’ve learned so far: Drs. Schnitt and Tung have completed a randomized phase II clinical trial called INFORM (NCT01670500) to compare the efficacy of cisplatin and standard chemotherapy agents, doxorubicin and cyclophosphamide (AC), in women with early-stage breast cancer who have inherited BRCA1/2 mutations. The INFORM study showed that:
- Cisplatin is active in treating breast cancer in BRCA mutation carriers.
- Patients with TNBC or ER-positive BRCA-associated breast cancer did not respond better to cisplatin than to AC.
- Tumor responses seen are due to DNA damaging chemotherapy in general, and not specifically cisplatin.
What’s next: Drs. Schnitt and Tung will analyze specimens from the INFORM trial to identify molecular markers that distinguish those who do better on cisplatin compared to AC, standard chemotherapy treatment. The team plans to use artificial intelligence to evaluate pre-treatment tumor specimens to explore whether there are indicators of which tumors will respond well to treatment.
Stuart J. Schnitt, M.D. 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, co-leader of the Dana Farber Harvard Cancer Center Breast Program, Senior Pathologist at Brigham and Women’s Hospital, a Professor of Pathology at Harvard Medical School and an internationally recognized expert in breast pathology.
Dr. Schnitt did 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 Beth Israel Hospital/Beth Israel Deaconess Medical Center Department of Pathology from 1984-2017, including 11 years as Director of Anatomic Pathology and subsequently Vice Chair for Anatomic Pathology. He has published over 350 original articles, review articles, editorials, commentaries, and book chapters, primarily in the area of breast diseases. He has authored a popular breast pathology textbook entitled “Biopsy Interpretation of the Breast”, now its third edition. The first two editions of this book were also published in Chinese. In addition, he is one of the editors of the 4th and 5th Editions of the “World Health Organization Classification of Tumours of the Breast”, published in 2012 and 2019, respectively.
Dr. Schnitt is a Past President of the United States and Canadian Academy of Pathology (2010-2011). Other notable honors include the Arthur Purdy Stout Society of Surgical Pathologists Annual Prize (1999), the Albany Medical College Distinguished Alumnus Award (2014), the Lynn Sage Distinguished Lecturer (2014), the Maude Abbot Lecture at the United States and Canadian Academy of Pathology Annual Meeting (2016), the United States and Canadian Academy of Pathology F.K. Mostofi Distinguished Service Award (2018), the United States and Canadian Academy of Pathology Harvey Goldman Teaching Award (2019), and the International Society of Breast Pathology-Breast Cancer Research Foundation Larry Norton, MD Award (2019). He is particularly proud to have been involved in the training of 39 breast pathology fellows since 1995. He has lectured extensively around the world. His research interests and contributions to our understanding of benign breast diseases and breast 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.