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Kenneth Offit, MD, MPH
Robert and Kate Niehaus Chair in Inherited Cancer Genomics
Chief, Clinical Genetics Service
Vice Chairman, Academic Affairs
Department of Medicine,
Memorial Sloan Kettering Cancer Center
Member, Cancer Biology and Genetics Program,
Sloan Kettering Institute
New York, New York
Goal: To identify new causes of inherited breast and ovarian cancer and to increase knowledge and awareness of personal familial risk.
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 continue their work studying targeted drugs that may benefit people who have inherited mutations in genes other than the well-known BRCA genes and are exploring strategies for effective, population-wide genetic screening.
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. Additionally, he is working to increase awareness and expand testing for those with familial risk of breast and ovarian cancer.
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 investigation: 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: His team has discovered a rare inherited cause of breast cancer involving mutations in the nucleotide excision pathway—DNA repair process. They have created a laboratory model and have successfully targeted this mutation with several drugs. Additionally, using a database of 27,000 patients with advanced cancer who have had DNA sequencing, they have created and published an algorithm to automate 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. Dr. Offit is also exploring novel approaches to larger, population-wide screening for genetic risks for cancer.
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.