Abstract PS3-05-05: High-risk cancer susceptibility genes mutation carriers’ compliance with surgical risk reduction for breast and ovarian cancer

Abstract Background Identifying pathogenic/likely pathogenic variants in high-risk cancer genes is key to cancer risk management.Prophylactic surgeries like RRM and RRSO are guideline-recommended options. This study aims to provide real-world evidence on their clinical implementation. Methods Between 2020 and 2025, 203 women referred for genetic testing at Genekor Medical S.A., were detected with P/LP variants in cancer susceptibility genes, for which risk-reducing surgical options are either recommended or considered for discussion. Referring clinicians were invited to complete a questionnaire to assess whether prophylactic surgical options had been discussed, if the patients had agreed to undergo such procedures, and whether the surgeries have already been performed or postponed. Results Among the individuals referred for genetic testing, 168(83%) were referred following a cancer diagnosis, while 35(17%) were unaffected individuals referred due to a family history. 153 individuals (76%) harbored BRCA1/2, 31(15%) harbored PALB2, PTEN, TP53 and 19 (9%) harbored BRIP1,RAD51C, RAD51D P/LP variants. RRSO was discussed with 78/153 (51%) of BRCA1/2 carriers and agreed in 60/78 (77%) cases. Addition of hysterectomy to RRSO was discussed in 16/78 (21%) of cases and agreed in 10/16 (63%). RRM was discussed with 113/203 (56%) of patients and agreed in 73/113(65%). In PALB2, PTEN, TP53 carriers, RRM was discussed in 21/31 (68%) cases, and accepted in 9/21 (43%), while in 5 cases both RRM/RRSO were discussed with 3 women agreeing. Finally, for 19 BRIP1,RAD51C, RAD51D carriers, in 9 cases the physician discussed RRSO as an option, with the examinees agreeing in 7 of them and in 5 cases RRM was discussed with agreement to proceed in 2 of them. In all cases, 22 individuals although agreed to proceed with RRM and/or RRSO, decided to postpone the procedure. Conclusions This study highlights the high awareness and acceptance of surgical management demonstrating the adherence to the recommendations. Age under 35 years and receiving therapy at the time of genetic testing were significant factors in lowering risk reduction RRSO and hysterectomy performance rates. Stage IV cancer was the main reason for not discussing surgical intervention. Citation Format: K. Papazisis, M. Paraskeva, S. Giassas, M. Skondra, R. Iosifidou, C. Tolis, G. Kesisis, E. Zairi, V. Venizelos, C. Markopoulos, I. Natsiopoulos, E. Bleka, I. Xanthakis, A. Ananiadis, D. Matheos, D. Stefanou, A. Adamidis, A. Meintani, G. Kapetsis, D. Bouzarelou, E. Papadopoulou, G. Nasioulas. High-risk cancer susceptibility genes mutation carriers’ compliance with surgical risk reduction for breast and ovarian cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-05-05.