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Kenneth Offit, MD, MPH
Co-Head, Program in Cancer Prevention, Control and Population Research
Memorial Sloan Kettering Cancer Center
Professor of Medicine and Public Health,
Weill Cornell Medical College
New York, New York
Goal: To identify new causes of inherited breast and ovarian cancer.
Impact: Dr. Offit and his colleagues are conducting several studies of inherited mutations that drive breast and ovarian cancer. They have discovered a rare inherited cause of breast cancer and a type of therapy that may benefit affected patients. Their work continues to add to our understanding of the genetic risk of breast cancer and inform more personalized strategies for preventing and treating the disease.
What’s next: The team will complete their study of their internet-assisted testing program. They will also continue to search for targeted drugs that may benefit people who have inherited mutations in genes other than the well-known BRCA genes.
The most well-known genes implicated in inherited breast and ovarian cancer susceptibility are BRCA1 and BRCA2. However, there are other, less common inherited gene mutations that drive these diseases that are not as well understood. Dr. Offit’s research is aimed at discovering these other mutations, determining the risk they pose, and identifying drugs that target them.
Full Research Summary
Research area: Understanding the causes of hereditary breast cancer beyond the BRCA genes.
Impact: In addition to the BRCA genes, there are many other genes that, when mutated, predispose women and men to breast cancer. Dr. Offit and his colleagues are conducting studies to identify other genes involved hereditary breast cancer. They have identified a new mechanism of breast cancer susceptibility and hope to identify drug targets for treatment in patients affected.
Current research: Dr. Offit’s team is conducting a series of studies aimed at identifying new causes of hereditary breast and ovarian cancer and identifying potential drug targets.
What he’s learned so far: Dr. Offit’s team has discovered a rare inherited cause of breast cancer involving mutations in the nucleotide excision pathway – a DNA repair process. They have created a laboratory model and are utilizing it to target this mutation with several drugs. Using a database of 27,000 patients with advanced cancer who have had DNA sequencing, they have automated the interpretation of the vast amount of DNA sequence data necessary to make future mutation discoveries.
What’s next: They will continue their efforts to identify other drug targets of the nucleotide excision pathway and validates these findings in laboratory studies.
Kenneth Offit is Chief of the Clinical Genetics Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center (MSKCC). He is also Professor of Medicine and Public Health at Weill Medical College of Cornell University, and Vice Chairman of the Program in Prevention, Control and Population Research at MSKCC. He received his AB at Princeton University and his MD and MPH from the Harvard Medical School and the Harvard School of Public Health. He is a member of the American Society for Clinical Investigation. He was awarded an American Cancer Society Career Research Recognition Award and the 2013 ASCO American Cancer Society Award for research in cancer prevention. Dr Offit is a member of the Board of Scientific Counselors of the National Cancer Institute, and of the Evaluation of Genomic Applications in Practice and Prevention working group of the U.S. Centers for Disease Control.
Dr. Offit's research team identified the most common mutation associated with hereditary breast and ovarian cancer in those of Ashkenazi Jewish ancestry. His group also published the first prospective study documenting a decreased risk of breast and ovarian cancer following oophorectomy in women carrying inherited mutations of the BRCA genes, and the first genome wide association study of BRCA2 mutation carriers. Dr Offit's group has discovered or characterized inherited mutations associated with risk of breast, ovarian, colon cancer, non-Hodgkin's lymphoma, and other malignancies. His laboratory currently focuses on utilizing genomic approaches to discover novel mechanisms associated with increased risk for common malignancies, or which modify the risks of known hereditary predispositions.