Titles and Affiliations
Chief, Breast Medicine Service
Professor of Medicine,
Weill Cornell Medical College
Research area
Understanding how genes influence breast cancer risk to guide personalized screening and risk reduction strategies.
Impact
Most breast cancers are not the result of inherited mutations in cancer causing genes. For families with a high incidence of breast cancer, however, a genetic component may underlie an increased risk. The BRCA genes (BRCA1 and BRCA2) are the most common heritable risk genes, but scientists have uncovered many more genes that may be implicated in an increased risk of breast cancer. Testing for mutations in BRCA1, BRCA2, and other susceptibility genes has become nearly routine, and will become more so in the years to come. Despite this, there is little guidance available to doctors in how to provide the best care for women with a genetic susceptibility to breast cancer. Dr. Robson and his team employ advanced technologies that incorporate information from genetic tests to enhance the precision of genetic risk assessment in women with mutations in BRCA or other susceptibility gene. This includes utilizing genomic markers to create a risk modifying panel, called polygenic risk score (PRS) to help women gain a better understanding of their breast cancer risk which can lead to more informed decisions about their preventive and screening care.
Progress thus far
Over the past year, Dr. Robson has continued to develop the use of PRS to provide more specific, personalized risk estimates for women with inherited mutations in BRCA1/BRCA2 and other breast cancer risk genes. The team has completed accrual of the BRCA cohort and are now modifying the assay to allow them to provide similar estimates for women in CHEK2, ATM, and PALB2.
Dr. Robson and his team have also developed a new blood test method that can detect tiny amounts of circulating tumor DNA (ctDNA)- fragments of DNA shed by tumors that circulate in the blood. Early results from this innovative test show promise in detecting early-stage breast cancer and monitoring how well treatment works. This non-invasive approach could significantly improve early cancer detection and treatment tracking, benefiting many women who carry genetic risk. The team plans to continue to develop this new technology, using it to track the effectiveness of treatments and assess whether it might be superior to conventional imaging approaches. It has potential particularly in women with BRCA mutations because of the specific nature of the DNA changes in BRCA-associated cancers.
What’s next
In the coming year, Dr. Robson plans to significantly advance the PRS research by expanding participant recruitment to include women with mutations in moderate-risk genes such as CHEK2, ATM, and PALB2. Participants will undergo comprehensive genetic testing using their enhanced PRS assay, which integrates an expanded panel of genetic variants. This improved PRS assay, combined with clinical and familial risk factors through the CANRISK model, will provide more precise individualized risk assessments. Dr. Robson and team will evaluate the impact of these personalized risk estimates on women’s decisions about preventive care strategies. Additionally, the team will enhance their novel ctDNA platform, specifically for early-stage ER-positive/HER2-negative breast cancer, refining their methods and analytical tools to improve the sensitivity and specificity of ctDNA detection. This effort addresses a significant clinical need, as this subtype of breast cancer is challenging to monitor with current diagnostic tools.
Biography
Mark E. Robson, MD is an Associate Attending Physician of the Clinical Genetics and Breast Medicine Service in the Department of Medicine at Memorial Sloan Kettering Cancer Center. He received his BSc from Washington and Lee University and his MD from the University of Virginia. He performed residency and fellowship training at Walter Reed Army Medical center before coming to Memorial Sloan Kettering in 1996. He is currently the Clinic Director of the Clinical Genetics Service and the chair of the Cancer Genetics Subcommittee of the American Society of Clinical Oncology.
Dr. Robson’s research is directed toward the improving the integration of genetic information into the clinical management of women with breast cancer. He and his colleagues have conducted a number of studies examining outcomes in women with hereditary breast cancer to better define the risks and benefits of treatments such as breast conserving therapy and adjuvant chemotherapy in this group. He and his coworkers have also conducted a number of studies examining the effectiveness of screening interventions such as breast MRI or ovarian cancer screening in women at hereditary risk. He is currently conducting studies to evaluate the impact of intensive screening or surgical prevention upon women’s quality of life, and to develop new screening tools, such as serum peptide profiling.
