Clinical Genetics Service, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Manchester Centre for Genomic Medicine, Central Manchester NHS Foundation Trust, Manchester, UK.
J Med Genet. 2022 Feb;59(2):133-140. doi: 10.1136/jmedgenet-2020-107356. Epub 2021 Feb 10.
Women testing positive for pathogenic variants have high lifetime risks of breast cancer (BC) and ovarian cancer. The effectiveness of risk reducing surgery (RRS) has been demonstrated in numerous previous studies. We evaluated long-term uptake, timing and effectiveness of risk reducing mastectomy (RRM) and bilateral salpingo-oophorectomy (RRSO) in healthy carriers.
Women were prospectively followed up from positive genetic test (GT) result to censor date. χ² testing compared categorical variables; Cox regression model estimated HRs and 95% CI for BC/ovarian cancer cases associated with RRS, and impact on all-cause mortality; Kaplan-Meier curves estimated cumulative RRS uptake. The annual cancer incidence was estimated by women-years at risk.
In total, 887 women were included in this analysis. Mean follow-up was 6.26 years (range=0.01-24.3; total=4685.4 women-years). RRS was performed in 512 women, 73 before GT. Overall RRM uptake was 57.9% and RRSO uptake was 78.6%. The median time from GT to RRM was 18.4 months, and from GT to RRSO-10.0 months. Annual BC incidence in the study population was 1.28%. Relative BC risk reduction (RRM versus non-RRM) was 94%. Risk reduction of ovarian cancer (RRSO versus non-RRSO) was 100%.
Over a 24-year period, we observed an increasing number of women opting for RRS. We showed that the timing of RRS remains suboptimal, especially in women undergoing RRSO. Both RRM and RRSO showed a significant effect on relevant cancer risk reduction. However, there was no statistically significant RRSO protective effect on BC.
检测到致病性变体呈阳性的女性患乳腺癌（BC）和卵巢癌的终生风险很高。大量先前的研究已经证明了降低风险手术（RRS）的有效性。我们评估了健康携带者中降低风险的乳房切除术（RRM）和双侧输卵管卵巢切除术（RRSO）的长期接受程度、时机和有效性。
从阳性基因检测（GT）结果到截止日期对女性进行前瞻性随访。卡方检验比较分类变量；Cox 回归模型估计与 RRS 相关的 BC/卵巢癌病例的 HR 和 95%CI，并评估对全因死亡率的影响；Kaplan-Meier 曲线估计累积 RRS 接受率。通过风险妇女的年数估计每年的癌症发病率。
总共 887 名女性纳入本分析。平均随访时间为 6.26 年（范围=0.01-24.3；总=4685.4 名妇女年）。512 名女性接受了 RRS，其中 73 名在 GT 之前。总体 RRM 接受率为 57.9%，RRSO 接受率为 78.6%。从 GT 到 RRM 的中位时间为 18.4 个月，从 GT 到 RRSO 的中位时间为 10.0 个月。研究人群中每年 BC 的发病率为 1.28%。RRM 与非 RRM 相比，BC 的相对风险降低（RRM 与非 RRM）为 94%。RRSO 与非 RRSO 相比，卵巢癌的风险降低为 100%。
在 24 年的时间里，我们观察到越来越多的女性选择接受 RRS。我们表明，RRS 的时机仍然不理想，尤其是在接受 RRSO 的女性中。RRM 和 RRSO 均对降低相关癌症风险具有显著效果。然而，RRSO 对 BC 没有统计学上显著的保护作用。
