AB026. SOH24AB_045. Knowledge of BRCA1/BRCA2 pathogenic variant status in a non-Ashkenazi Jewish cohort is important for survival

Background: BRCA1/2 pathogenic variant carriers have a higher lifetime risk of developing breast cancer. Risk-management options include breast surveillance or bilateral prophylactic mastectomy (BPM). The aim of this study was to assess if knowledge of one's pathogenic variant status is important for survival. Methods: A single-centre, retrospective observational cohort study was undertaken. Patients identified as having a high risk of breast cancer based on family history between January 2008–2023 were included (n=1,411). Patients were identified based on their lifetime risk of disease being calculated as greater than 30% using the Tyrer-Cuzick model (IBIS tool), no known BRCA pathogenic variant in their family and no personal history of disease. Results: Breast cancer developed in 168 patients. Patients who underwent BPM did not develop breast cancer (n=77). Most BRCA carriers did not receive genetic testing until after their breast cancer diagnosis (147/168, 87.5%). Patients with a known BRCA germline pathogenic variant, identified prior to breast cancer diagnosis, were significantly more likely to have an immediate contralateral prophylactic mastectomy, which was prognostically favourable (P=0.023). Kaplan-Meier survival analysis illustrated that patients in the known genetic status cohort had improved overall survival (OS) (log rank P=0.043). At a median follow-up of 6.17 years, all patients in this cohort were still alive. Conclusions: A more widespread approach to testing should be considered in this non-Ashkenazi Jewish high-risk family history cohort to optimise and personalise the risk-management options available to each patient. Knowledge of BRCA1/BRCA2 carrier status in a non-Ashkenazi Jewish cohort is important for survival.