Clinic Director, Clinical Genetics Service
Department of Medicine
Memorial Sloan Kettering Cancer Center
New York, New York
Seeking new tools to improve the accuracy of risk prediction in BRCA1 and BRCA2 mutation carriers.
Efforts are ongoing to validate a risk prediction score that refines the assessment of BRCA-associated risk of breast cancer.
These efforts will lead to a more personalized risk assessment in high-risk families.
Two decades after the initial identification of BRCA1 and BRCA2, considerable uncertainty remains regarding cancer risks associated with inherited mutations of these genes, as well as newly discovered cancer predisposition genes.
Drs. Robson and Offit are part of an international consortium called CIMBA to identify genetic "protective factors" that modify risk of breast cancer from BRCA2 mutations. They combined these "protective factors" with other genomic markers to define a risk modifying panel to more precisely assess risk in BRCA2 mutation carriers. Knowing the pattern of these variants permits the construction of a “polygenic risk score” or PRS, which could be used to determine the true level of BRCA-associated breast cancer risk.
Another component of this project is an internet-based patient portal called PROMPT aimed at improving risk assessment of newly discovered cancer risk genes. This is an online registry for individuals who underwent gene panel testing. Patients agree to be contacted for surveys and to contribute family information, as well as invite family members to take part.
This year, the team will conduct a survey of individuals with mutations in CDH1, a gene that predisposes people to both breast and stomach cancer. These efforts will lead to a more personalized risk assessment in high-risk families in an era in which technology continues to accelerate the discovery of new cancer susceptibility genes and the use of gene panel testing is becoming more common.
Mark 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 B.Sc. 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.