Clinical impact of germline <i>BRCA1/2</i> variants on breast and ovarian cancer management in a resource-limited setting: Real-world data from Thailand.

Abstract

e22654 Background: Identification of germline BRCA1/2 variants is critical for guiding the management of breast and ovarian cancer, including surveillance, prophylactic surgery, targeted therapy, and prevention. However, data regarding the clinical implementation of these strategies in resource-limited settings remain scarce. We aimed to evaluate the real-world clinical impact of BRCA1/2 status on patient management—specifically surveillance, risk-reducing surgery, and PARP inhibitor utilization—at a major tertiary center in Thailand. Methods: We performed a retrospective analysis of electronic medical records for index patients with breast cancer who underwent germline genetic testing at Siriraj Hospital, Bangkok. We assessed clinical outcomes among patients identified with pathogenic or likely pathogenic (P/LP) BRCA1/2 variants. Data collection included operative history, pathology, imaging utilization, and systemic therapy. Key endpoints were the utilization rates of breast MRI, contralateral prophylactic mastectomy (CPM), risk-reducing bilateral salpingo-oophorectomy (rrBSO), and poly (ADP-ribose) polymerase (PARP) inhibitors. Results: Of 6,138 patients undergoing germline genetic testing, 278 (4.5%) harbored P/LP BRCA1/2 mutations. Among carriers with non-metastatic disease (n=253), genetic results were available pre-operatively in only 38% of cases, limiting immediate surgical decision-making. In the specific subgroup of non-metastatic carriers with &gt;3 years of follow-up (n=81; median follow-up 4.7 years), 41% underwent contralateral prophylactic mastectomy (CPM). In contrast, high-sensitivity surveillance was minimal: 2% underwent breast MRI monitoring, with the remainder relying on mammography and ultrasonography. For ovarian cancer risk reduction among patients aged ≥40 years, 85% received a gynecologic consultation, and 63% successfully underwent risk-reducing bilateral salpingo-oophorectomy (rrBSO). In the metastatic setting (n=42), PARP inhibitors were used in 19% of cases (n=8), with cost being the most frequently cited barrier to access. Conclusions: While the prevalence of BRCA1/2 mutations in this Thai cohort mirrors international data, clinical management deviates significantly from Western guidelines due to resource constraints. Specifically, access to high-cost surveillance (MRI) and targeted therapies (PARP inhibitors) remains minimal. These findings highlight a critical need to improve pre-operative testing turnaround times and address the financial toxicity that restricts access to standard-of-care therapies in resource-limited settings.