BACKGROUND Risk-reducing salpingo-oophorectomy (RRSO) effectively prevents high-grade serous carcinoma (HGSC) in BRCA1/2 germline pathogenic variant (GPV) carriers. Still, some women develop HGSC after RRSO without pathologic findings. This study assessed long-term incidence and risk factors for developing HGSC after RRSO without pathologic findings. METHODS BRCA1/2 GPV carriers were selected from Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) cohort. Follow-up data for HGSC after RRSO were obtained from the Dutch Nationwide Pathology Databank (PALGA) and confirmed by histopathological review. Cumulative incidence rates of HGSC were calculated using Kaplan-Meier analyses. Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with an increased risk of HGSC following RRSO without pathologic findings. RESULTS A total of 2519 women were included, with a median follow-up of 13.4 years (range: 0.0-27.6). The 20-years cumulative incidence rate of HGSC was 1.5% (95% CI: 0.0-2.1) for BRCA1 and 0.2% (95% CI: 0.0-1.4) for BRCA2 GPV carriers. All women who developed HGSC underwent RRSO after the recommended age. Incomplete embedding of the RRSO specimen (HR: 4.2, 95% CI: 1.4-12.6), higher age at RRSO (HR per year: 1.1, 95% CI: 1.0-1.1), and carrying a BRCA1 GPV (HR: 12.1, 95% CI: 1.6-91.2) were associated with increased risk of HGSC. CONCLUSIONS In BRCA1/2 GPV carriers, long-term incidence of HGSC after RRSO without pathologic findings was low. Strict adherence to guidelines regarding timely RRSO followed by complete specimen embedding can further reduce the risk of HGSC in the years following RRSO.

中文翻译：

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BRCA1/2 种系致病性变异携带者在降低风险的输卵管卵巢切除术后发生的高级别浆液性癌。


背景 降低风险的输卵管卵巢切除术 （RRSO） 可有效预防 BRCA1/2 种系致病性变异 （GPV） 携带者中的高级别浆液性癌 （HGSC）。尽管如此，一些女性在 RRSO 后发生 HGSC 而没有病理发现。本研究评估了 RRSO 后发生 HGSC 的长期发病率和危险因素，但无病理发现。方法 从荷兰遗传性乳腺癌和卵巢癌 （HEBON） 队列中选择 BRCA1/2 GPV 携带者。RRSO 后 HGSC 的随访数据来自荷兰全国病理学数据库 （PALGA），并通过组织病理学审查确认。使用 Kaplan-Meier 分析计算 HGSC 的累积发病率。Cox 比例风险模型用于计算与 RRSO 后 HGSC 风险增加相关的因素的风险比 （HRs） 和 95% 置信区间 （CIss），而无病理发现。结果 共纳入 2519 名女性，中位随访 13.4 年 （范围：0.0-27.6）。BRCA1 和 BRCA2 GPV 携带者 HGSC 的 20 年累积发病率分别为 1.5% （95% CI： 0.0-2.1） 和 0.2% （95% CI： 0.0-1.4）。所有发生 HGSC 的女性在推荐年龄后接受了 RRSO。RRSO 标本包埋不完全 （HR： 4.2， 95% CI： 1.4-12.6）、RRSO 年龄较高 （HR/年： 1.1， 95% CI： 1.0-1.1） 和携带 BRCA1 GPV （HR： 12.1， 95% CI： 1.6-91.2） 与 HGSC 风险增加相关。结论 在 BRCA1/2 GPV 携带者中，RRSO 后无病理发现的 HGSC 长期发生率较低。严格遵守有关及时 RRSO 然后完全标本包埋的指南可以进一步降低 RRSO 后几年内发生 HGSC 的风险。