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 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 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 preventive and screening care.
The overarching goal of the project is to improve the monitoring 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, Dr. Robson is conducting a study to see whether giving women PRS-adjusted risk estimates helps them feel more comfortable with their prevention decisions. Fellow BCRF investigators Drs. Susan Domchek and Judy Garber are now also enrolling patients in the study to increase the number of participants.
A second component of Dr. Robson’s research is an evaluation of PARP inhibitor resistance in women with BRCA mutations who are receiving these drugs for metastatic disease. The team has collected samples and begun to identify genetic factors that may be causing resistance. They are now conducting analyses of circulating tumor DNA (ctDNA) that has been collected from women at various points before and after treatment, including those treated with PARP inhibitors. Taken together, these samples should allow deep exploration of the mechanisms and timing of PARP inhibitor resistance and ultimately inform new therapeutic strategies to improve outcomes.
In the coming year, Dr. Robson will continue to accrue participants to the PRS study in collaboration with Drs. Susan Domchek and Judy Garber. Dr. Robson anticipates completing this project in the next year. He and his team will also continue to accrue patients to the PARP inhibitor study and sequence samples from women pre- and post-PARP inhibitor therapy. Lastly, Dr. Robson is beginning a third project assessing a new ctDNA analysis technique to detect early-stage and recurrent breast cancer. He will test this technology in patients with BRCA mutant early-stage tumors.
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.
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