High-Risk Cancer Susceptibility Gene Mutation Carriers’ Compliance with Surgical Risk Reduction for Breast and Ovarian Cancer

Background: Risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) are established strategies for women carrying pathogenic or likely pathogenic (P/LP) variants in high-risk cancer susceptibility genes. However, real-world uptake remains variable and is influenced by clinical, demographic, and psychosocial factors. This study evaluated adherence to guideline-recommended surgical risk-reduction strategies following positive genetic testing. Materials and Methods: We conducted a retrospective observational study of 13,069 women who underwent hereditary cancer testing using a multigene next-generation sequencing panel between 2020 and 2025. Among them, 1,255 carriers of P/LP variants in genes with established recommendations for RRM and/or RRSO were identified. Physician-reported questionnaires were available for 203 individuals and captured data on counseling, acceptance, and implementation of risk-reducing surgery. Genes were grouped according to NCCN guideline recommendations: (i) BRCA1/2; (ii) PALB2, PTEN, TP53; and (iii) BRIP1, RAD51C, RAD51D. Results: Of the 203 women, 83% had a personal history of cancer. Overall, 83.7% were offered at least one risk-reducing intervention, with 64.9% accepting. RRM was more frequently discussed in higher breast cancer–risk genes, while RRSO discussion varied by gene group; these differences were statistically significant. Acceptance rates were moderate for RRM but consistently high for RRSO across groups. Younger age and advanced-stage disease were key factors limiting uptake or discussion, and 22 patients postponed surgery despite initial agreement. Conclusions: In this real-world cohort, physician counseling largely aligned with gene-specific guidelines, and acceptance of risk-reducing surgery was high once discussed, particularly for RRSO. However, uptake was influenced by age, disease stage, and clinical context. These findings highlight the importance of early genetic testing and multidisciplinary counseling to optimize timely decision-making and improve adherence to preventive strategies.