The Christie NHS Foundation Trust, Manchester, UK.
Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Eur J Hum Genet. 2020 Nov;28(11):1541-1547. doi: 10.1038/s41431-020-0692-y. Epub 2020 Jul 10.
Poly(ADP-ribose) polymerase (PARP) inhibitors improve survival in BRCA-mutant high-grade serous ovarian carcinoma. As a result, germline and somatic BRCA1/2 testing has become standard practice in women diagnosed with ovarian cancer. We outline changes in testing and detection rates of germline BRCA1/2 pathogenic variants (PVs) in cases of non-mucinous epithelial ovarian cancer diagnosed during three eras, spanning 12 years, within the North West of England, and compare the uptake of cascade testing in families identified by oncology-led mainstreaming versus regional genetics clinics. Eras included: Period 1 (20% risk threshold for testing): between January 2007 and May 2013; Period 2 (10% risk threshold for testing): between June 2013 and October 2017 and; Period 3 (mainstream testing): between November 2017 and November 2019. A total of 1081 women underwent germline BRCA1/2 testing between January 2007 and November 2019 and 222 (20.5%) were found to have a PV. The monthly testing rate increased by 3.3-fold and 2.5-fold between Periods 1-2 and Periods 2-3, respectively. A similar incidence of germline BRCA1/2 PVs were detected in Period 2 (17.2%) and Period 3 (18.5%). Uptake of cascade testing from first-degree relatives was significantly lower in those women undergoing mainstream testing compared with those tested in regional genetics clinics (31.6% versus 47.3%, P = 0.038). Mainstream testing allows timely detection of germline BRCA1/2 status to select patients for PARP inhibitors, but shortfalls in the uptake of cascade testing in first-degree relatives requires optimisation to broaden benefits within families.
聚（ADP-核糖）聚合酶（PARP）抑制剂可改善 BRCA 突变型高级别浆液性卵巢癌患者的生存率。因此，对诊断为卵巢癌的女性进行种系 BRCA1/2 检测已成为标准做法。我们概述了在英格兰西北部，12 年间三个时期内非黏液性上皮性卵巢癌病例中种系 BRCA1/2 致病性变异（PV）检测率的变化，并比较了肿瘤主导的主流化与区域遗传学诊所确定的家族中级联检测的采用情况。这些时期包括：第 1 期（检测风险阈值为 20%）：2007 年 1 月至 2013 年 5 月；第 2 期（检测风险阈值为 10%）：2013 年 6 月至 2017 年 10 月；第 3 期（主流检测）：2017 年 11 月至 2019 年 11 月。共有 1081 名女性在 2007 年 1 月至 2019 年 11 月期间接受了种系 BRCA1/2 检测，其中 222 名（20.5%）检测到 PV。第 1 期到第 2 期和第 2 期到第 3 期的每月检测率分别增加了 3.3 倍和 2.5 倍。第 2 期（17.2%）和第 3 期（18.5%）检测到的种系 BRCA1/2 PV 发生率相似。与在区域遗传学诊所接受检测的女性相比，接受主流检测的女性中一级亲属的级联检测接受率明显较低（31.6%比 47.3%，P=0.038）。主流检测可及时检测种系 BRCA1/2 状态，从而选择 PARP 抑制剂的患者，但一级亲属中级联检测的采用率不足，需要进一步优化，以扩大家族内的获益。
