Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Department of Obstetrics and Gynaecology, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, UK.
Int J Cancer. 2021 Mar 1;148(5):1155-1163. doi: 10.1002/ijc.33378. Epub 2020 Nov 11.
Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is highly effective for the prevention of high-grade serous ovarian cancer (HGSOC) in BRCA1/2 pathogenic variant carriers (PVCs), but does not completely eliminate future risk of primary peritoneal cancer (PPC). The requirement to completely remove fallopian tubes at RRBSO and carefully exclude occult cancer/serous tubal intraepithelial carcinoma (STIC) lesions may not have been appreciated historically. We calculated rates of HGSOC and PPC in confirmed BRCA1/2 PVCs registered on the regional database in those who did (cases) and did not (controls) undergo RRBSO after genetic testing. Expected annual rates of ovarian/peritoneal cancer were 1% for BRCA1 ≥ 35 years and 0.5% for BRCA2 ≥ 45 years. Follow-up before 35/45 years was "risk free" and lead time excluded RRBSO <35 years and <45 years for BRCA1 and BRCA2, respectively. Women were followed from personal mutation report (controls) or RRBSO (cases) to death, ovarian/peritoneal cancer or last follow-up, whichever was sooner. In total, 891 cases (BRCA1 = 468, BRCA2 = 423) and 1302 controls had follow-up ≥35 years (BRCA1 = 736) and ≥45 years (BRCA2 = 566), respectively, over a total of 7261.1 risk eligible years (mean = 8.15 years). Twenty-one occult ovarian cancers were found at RRBSO (2.4%), 16 at stage 1. Post RRBSO, 56.97 ovarian/peritoneal cancers were expected but only 3 were observed (HR = 0.053; 95% CI = 0.013-0.14), with combined Kaplan-Meier analysis HR = 0.029 (95% CI = 0.009-0.100, P < .001). Risk reduction was greater in specialist (HR = 0.03; 95% CI = 0.001-0.13) compared to non-specialist centres (HR = 0.11; 95% CI = 0.02-0.37) (P = .07). In controls, 23.35 ovarian/peritoneal cancers were expected with 32 observed (HR = 1.37; 95% CI = 0.95-1.91). RRBSO <35/<45 years reduces the risk of ovarian/peritoneal cancer by 95% in BRCA1/2 PVCs and may be greater in specialist centres.
风险降低的双侧输卵管卵巢切除术（RRBSO）对于 BRCA1/2 致病变异携带者（PVCs）预防高级别浆液性卵巢癌（HGSOC）非常有效，但并不能完全消除原发性腹膜癌（PPC）的未来风险。在 RRBSO 中完全切除输卵管并仔细排除隐匿性癌症/输卵管上皮内癌（STIC）病变的要求在历史上可能没有被认识到。我们计算了在基因检测后接受（病例）和未接受（对照组） RRBSO 的已确诊 BRCA1/2 PVCs 在区域数据库中登记的 HGSOC 和 PPC 的发生率。BRCA1 ≥ 35 岁的卵巢/腹膜癌的预期年发生率为 1%，BRCA2 ≥ 45 岁的预期年发生率为 0.5%。35/45 岁之前的随访是“无风险”的，排除了 RRBSO <35 岁和 BRCA1 <45 岁，以及 RRBSO <45 岁和 BRCA2 <45 岁。女性从个人突变报告（对照组）或 RRBSO（病例）开始随访至死亡、卵巢/腹膜癌或最后一次随访，以先发生者为准。总共 891 例病例（BRCA1 = 468，BRCA2 = 423）和 1302 例对照者的随访时间均≥35 岁（BRCA1 = 736）和≥45 岁（BRCA2 = 566），随访时间总计为 7261.1 年（平均 8.15 年）。在 RRBSO 中发现了 21 例隐匿性卵巢癌（2.4%），其中 16 例处于 1 期。RRBSO 后，预计会发生 56.97 例卵巢/腹膜癌，但仅观察到 3 例（HR = 0.053；95%CI = 0.013-0.14），结合 Kaplan-Meier 分析 HR = 0.029（95%CI = 0.009-0.100，P < 0.001）。与非专科中心相比（HR = 0.11；95%CI = 0.02-0.37），专家中心的风险降低更大（HR = 0.03；95%CI = 0.001-0.13）（P = 0.07）。在对照组中，预计会发生 23.35 例卵巢/腹膜癌，而观察到 32 例（HR = 1.37；95%CI = 0.95-1.91）。BRCA1/2 PVCs 中 RRBSO <35/<45 岁可使卵巢/腹膜癌风险降低 95%，在专家中心可能会更大。
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