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
Dana-Farber Cancer Institute/Brigham and Women's Cancer Center
Boston, Massachusetts

Research area

Determining predictors of chemotherapy response in BRCA-driven breast cancers.

Impact

The BRCA1 and BRCA2 genes are the most commonly mutated genes in hereditary breast and ovarian cancers. Normally, BRCA 1 and BRCA2 function to ensure the proper repair of DNA damage, but mutations in these genes lead to rapid accumulation of DNA errors, which is the underlying cause of cancer. However, this defect also makes BRCA-mutated cells vulnerable to treatments that cause DNA damage. Drs. Schnitt and Tung are working to understand the unique characteristics of breast tumors from patients with inherited BRCA1 or BRCA2 mutations to identify predictors of response and resistance to chemotherapy and ultimately improve treatment strategies for BRCA-driven breast and ovarian cancers.

Progress Thus Far

Drs. Schnitt and Tung are identifying features of breast tumors that predict response to chemotherapy in BRCA-driven breast cancers. The team completed the INFORM trial, which demonstrated that cisplatin is an active chemotherapy in BRCA mutation carriers with breast cancer. While they did not find it to be more effective than the standard chemotherapy regimen, it provides another treatment option for patients. Drs. Schnitt and Tung are analyzing blood and tumor specimens collected from INFORM participants to better understand the molecular landscape of these cancers and to discover biomarkers of response to cisplatin and standard chemotherapy. So far, they found through genomic analysis that 89 percent of breast cancers in BRCA carriers have lost one copy of the gene and its surrounding region on the chromosome. They have also found some tumors that each have hundreds of chromosomal rearrangements in one or several regions, which are highly associated with resistance to chemotherapy.

What’s next

In the upcoming year, Drs. Schnitt and Tung will continue performing genomic analyses to probe more deeply into chromosomal rearrangements, evaluating on which chromosomes they occur, where on the chromosome they occur, and patterns of rearrangement. They will also continue analysis of INFORM biospecimens to determine genetic predictors of chemotherapy response and to identify mutations that could affect the efficacy of PARP inhibitors, which are commonly used to treat BRCA-driven breast cancers. Finally, Drs. Schnitt and Tung will continue to work on an artificial intelligence model for response to chemotherapy. Towards this end, they plan to explore whether any clinical variables (tumor stage, patient age, etc.) increase the accuracy of the model generated from pathology features, then test the model on data from an independent cohort of patients from another clinical trial.

Biography

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.

BCRF Investigator Since

2007

Donor Recognition

The Joan Lunden Award

Areas of Focus

Co-Investigator