Memorial Sloan Kettering Cancer Center New York, New York
Chief, Breast Medicine Service Professor of Medicine, Weill Cornell Medical College
Understanding how genes influence breast cancer risk and developing more precise risk estimates to guide personalized screening and risk reduction strategies.
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 inherited risk. The BRCA genes (BRCA1 and BRCA2) are the most common of these inherited mutations, 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 a BRCA or other susceptibility gene. This includes utilizing genomic markers to define 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 care.
The overarching goal of the project is to improve the care of women with an inherited predisposition to breast cancer. Dr. Robson’s earlier BCRF-supported work identified a number of genetic modifiers of breast cancer risk that can be combined into a polygenic risk score (PRS). The PRS also measures risk associated with BRCA1 or 2 mutations. Now, his team is conducting a study to see whether PRS-adjusted risk estimates help women with BRCA mutations make decisions about having routine screening versus having prophylactic mastectomy. The study has accrued 135 of a planned 195 women and is expected to finish enrollment this year.
A second component of Dr. Robson’s project is ongoing support of the Prospective Registry of MultiPlex Testing (PROMPT), a patient-directed online registry including nearly 10,000 individuals who have undergone multigene panel testing and found to have mutations in one or more cancer susceptibility genes. The project is looking at genetic changes that occur in the cancers of people with inherited predisposition due to mutations in genes like BRCA1, BRCA2, ATM, CHEK2, and PALB2.
In the upcoming grant year, Dr. Robson will continue his support of the PROMPT registry. The registry has already served as a source of participants for a number of important studies, and Dr. Robson will work to continue enlarging it. Dr. Robson also plans to continue to explore the genomics of PARP inhibitor resistance to improve our understanding of how resistance evolves, which can inform strategies to prevent resistance from occurring.
If not for BCRF, we would not be able to nimbly pursue new areas of research suggested by preliminary findings or novel hypotheses. The ability to move quickly is critical to assessing whether these new areas are promising. The generous support of BCRF helps us to rapidly respond and, by doing so, accelerate the translation of new observations towards the ultimate goal of curing breast cancer. –Dr. Robson
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.
2006
The Taub Family Award
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