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 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.
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, in collaboration with BCRF investigators Drs. Susan Domchek and Judy Garber, is conducting a study to see whether giving women PRS-adjusted risk estimates helps them feel more comfortable with their prevention decisions. This project has now completed accrual, with 353 women enrolled across three sites. Dr. Robson and team are now evaluating the impact of personalized information on decision making.
A second component of Dr. Robson’s research is to use ultra-sensitive liquid biopsy to identify circulating tumor DNA (ctDNA) in the blood of patients who have early-stage breast cancer with inherited BRCA mutations. Dr. Robson is taking advantage of advances in genetic sequencing technology to detect abnormal genetic signals, even when tumor tissue isn’t available for testing.
In the coming year, Dr. Robson will continue to accrue patients to the two main projects and include women with mutations in other high-risk genes such as ATM, CHEK2, and PALB2. This extension will address the important question of how to better inform women with more modifiable risks. Finally, Dr. Robson will continue to define parameters that will inform a subsequent screening study for early-stage BRCA-driven breast cancer.
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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