Pathogenic BRCA Variants in the Ashkenazi Jewish Population: A Retrospective Study [ID 2683559

Abstract

INTRODUCTION: Pathogenic variants in BRCA genes (BRCA-PV) increase risk for cancers. Established guidelines for BRCA-PV risk reduction include surveillance, chemoprevention, and surgery. Ashkenazi Jews (AJ) have increased prevalence of BRCA-PVs versus the general population: 1/40 versus 1/160. Population testing of AJs, testing based on ancestry alone, identifies more BRCA-PV carriers than testing based on family history. METHODS: Charts of 683 AJ patients tested in a gynecology office for BRCA-PVs between January 1, 2017, and June 30, 2020, were retrospectively reviewed for BRCA-PV status, history, and clinical management. Findings were compared to 2017 National Comprehensive Cancer Network (NCCN) guidelines, current at time of testing. Patients were appropriately counseled for clinical management. RESULTS: Six hundred eighty-three AJs, mean age 51.0±13.5 years, were tested for BRCA-PVs: 14 tested positive (2%), mean age 41.6±14.16; 13/14 (93%) were female. Of patients with PV, 6 (43%) patients did not qualify for screening based on 2017 guidelines. Of positive female patients, 7 (54%) chose risk-reducing bilateral salpingo-oophorectomy (rrBSO), 4 (31%) chose mastectomy, 3 (21%) chose in vitro fertilization with wild-type embryos. One patient was found to have invasive serous tubal cancer at rrBSO; another with ER− breast cancer with first screening MRI. CONCLUSION: Our study confirms increased BRCA-PV prevalence amongst AJs. Over half of individuals tested did not meet 2017 NCCN criteria, including two positive patients diagnosed with cancer—indicating that 2017 criteria did not capture at-risk individuals. Updated guidelines recommending BRCA-PV testing of AJs must be implemented to identify actionable PVs and initiate cancer prevention strategies.