Professor and Chair
Division of Experimental Pathology
Department of Laboratory Medicine and Pathology
Over 15 percent of women and men who develop breast cancer have one or more close relatives who also have had the disease, suggesting that these families have inherited mutations in high-risk breast cancer susceptibility genes. Individuals who inherit mutations in the BRCA1 breast cancer gene have, on average, a 65 percent chance of developing breast cancer and a 30 percent chance of ovarian cancer in their lifetime. However, there are great differences in the risks of cancer among BRCA1 mutation carriers. Dr. Couch’s BCRF research involves identification of inherited genetic alterations that modify the risk for breast cancer in BRCA1 mutation carriers and predispose to triple negative (ER-negative, PR-negative, HER2-negative) breast cancer. With generous support from BCRF and the involvement of over 20,000 people with inherited BRCA1 mutations and 4,000 with triple negative breast cancer, Dr. Couch and his colleagues have identified several genetic risk factors for breast and ovarian cancer. This study has now been extended to include 21,000 BRCA1 mutation carriers and a new method for investigating genetic alterations called the “Oncoarray”. The researchers expect this method will identify several additional risk factors which will provide a more personalized risk assessment among BRCA1 mutation carriers so that those at particularly high risk of cancer can act quickly to reduce their risk while those at much lower than expected risk can change their approach to the management of their risk. In addition, Dr. Couch is collaborating with other BCRF investigators (including James Ford, Judy Garber, Katherine Nathanson, Kenneth Offit and others) to identify new high-risk breast cancer genes that cause breast cancer that tracks through families. Many good possibilities have been selected and follow up studies to confirm those that substantially increase risk of breast cancer are underway. The results will prove useful for identifying people at significantly increased risk of this disease due to inherited mutations in these genes. In the next year they propose to 1) Identify common genetic risk factor modifiers for breast cancer that can be used for improved risk assessment for BRCA1 mutation carriers and triple negative breast cancer; and 2) discover new moderate and high-risk breast cancer susceptibility genes through genome sequencing of high-risk breast cancer families.
Fergus Couch is Professor and Chair of the Division of Experimental Pathology and Laboratory Medicine at the Mayo Clinic, with joint appointments in the Departments of Health Sciences Research and Biochemistry and Molecular Biology. Dr. Couch works on the genetics of breast cancer, with over 300 publications relating to the discovery and clinical characterization of inherited genetic variants in cancer susceptibility genes. He is the principal investigator of the Mayo Clinic Breast Cancer Registry and is a founder and a member of the coordinating committee of CIMBA (the consortium of investigators of modifiers of BRCA1/2) focused on identifying genetic modifiers of breast cancer risk in the BRCA1 carrier population. Similarly, he is the principal investigator of the Triple Negative Breast Cancer Consortium (TNBCC), aimed at understanding the genetic etiology of triple negative breast cancer, and is a long-term contributor to the international Breast Cancer Association Consortium (BCAC). Dr. Couch is a co-founder of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium focused on establishing the clinical relevance of variants of uncertain significance (VUS) in BRCA1/2. Within ENIGMA he is coordinating efforts to characterize the risk and penetrance of deleterious mutations and VUS in non-BRCA1/2 predisposition genes. He has also collaborated with investigators from Memorial Sloan Kettering Cancer Center and the University of Pennsylvania to develop the Prospective Registry Of Multi-Plex Testing (PROMPT) for patients with mutations in predisposition genes. Dr. Couch is a founding member and participant in COMPLEXO, a consortium aiming to identify additional breast cancer predisposition genes.