Retrospective Analysis of the Uptake and Timing of Risk-Reducing Salpingo-Oophorectomy in Women With BRCA1/2 Pathogenic Variants

对携带 BRCA1/2 致病变异的女性接受风险降低性输卵管卵巢切除术的接受情况和时机的回顾性分析

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Abstract

Introduction Risk-reducing salpingo-oophorectomy (RRSO) can substantially reduce ovarian cancer incidence in women carrying pathogenic BRCA1 or BRCA2 variants, which cause hereditary breast and ovarian cancer syndrome. The decision to undergo RRSO or continue surveillance is influenced by personal background and psychosocial factors, but the process in Japan has not been well studied. Even among women who ultimately choose RRSO, some proceed promptly, while others delay. This study aimed to identify factors associated with the decision to undergo RRSO and to examine the timing of that decision, specifically whether it occurred within 365 days of genetic testing. Methods We retrospectively reviewed records of patients who either (1) had breast cancer and were found to carry a BRCA1/2 pathogenic variant, or (2) had a family history and were confirmed as carriers. BRCA1/2 testing was performed using next-generation sequencing covering all coding regions and exon-intron boundaries, with confirmatory Sanger sequencing. Data collected included age at consultation, parity, history of breast cancer and treatment, genetic testing date and result, RRSO date, insurance coverage, pathology findings, and reasons for surveillance. Multivariable logistic regression assessed factors associated with undergoing RRSO and with undergoing RRSO within 365 days. Kaplan-Meier analysis and Cox regression were used to evaluate time-to-RRSO. Statistical significance was set at p < 0.05. Results A total of 70 patients were analyzed (mean age 47.8 years (SD 13.1); 55 (78.6%)) had breast cancer. Pathogenic variants were in BRCA1 (n=26, 37.1%) or BRCA2 (n=44, 62.9%). A total of 32 patients (45.7%) underwent RRSO. Multivariable analysis showed age >45 years (p = 0.0202, OR: 4.00, 95% CI: 1.24-12.9) and breast cancer history (p = 0.0247, OR: 7.68, 95% CI: 1.30-45.4) were significantly associated with RRSO. Among those undergoing RRSO within 365 days, BRCA1 carriers were more likely than BRCA2 carriers to have early surgery (p = 0.0471, OR: 6.81, 95% CI: 1.02-45.3). Kaplan-Meier analysis showed shorter median time to RRSO for BRCA1 carriers (565 days) vs. BRCA2 carriers (1,015 days); Cox regression findings were consistent. Conclusion Age and breast cancer history were important factors in the decision to undergo RRSO. Earlier RRSO among BRCA1 carriers suggests that genetic counseling effectively conveys their higher and earlier ovarian cancer risk. These results highlight the importance of individualized counseling that considers each patient's background, supporting informed decisions about both RRSO uptake and timing.

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