BRCA1 和 BRCA2 基因突变患者的风险降低输卵管卵巢切除术的吸收和时机。
Uptake and timing of risk-reducing salpingo-oophorectomy among patients with BRCA1 and BRCA2 mutations.
机构信息
Department of Obstetrics and Gynecology, New York University Langone Health, New York, NY.
Department of Population Health, New York University Langone Health, New York, NY.
出版信息
Am J Obstet Gynecol. 2021 Nov;225(5):508.e1-508.e10. doi: 10.1016/j.ajog.2021.06.070. Epub 2021 Jun 23.
BACKGROUND
In women with BRCA mutations, risk-reducing bilateral salpingo-oophorectomy has been shown to decrease gynecologic cancer-specific and overall mortality. The National Comprehensive Cancer Network recommends that patients with BRCA mutations undergo risk-reducing bilateral salpingo-oophorectomy between the ages of 35 and 40 years for BRCA1 mutation carriers and between the ages of 40 and 45 years for BRCA2 mutation carriers or after childbearing is complete. Currently, uptake and timing of risk-reducing bilateral salpingo-oophorectomy and reasons for delays in risk-reducing bilateral salpingo-oophorectomy are not well understood.
OBJECTIVE
We sought to evaluate uptake and timing of risk-reducing bilateral salpingo-oophorectomy among women with BRCA1 and BRCA2 mutations concerning the National Comprehensive Cancer Network guidelines and reasons for delays in risk-reducing bilateral salpingo-oophorectomy.
STUDY DESIGN
In this retrospective chart review, we identified women with BRCA1 and BRCA2 mutations who discussed risk-reducing bilateral salpingo-oophorectomy with a provider between 2012 and 2021. Uptake of risk-reducing bilateral salpingo-oophorectomy was documented, and patients were classified as having timely or delay in risk-reducing bilateral salpingo-oophorectomy based on the National Comprehensive Cancer Network guidelines. For those with delay in risk-reducing bilateral salpingo-oophorectomy, reasons cited for delay were collected. Comparative statistical analyses were performed to evaluate characteristics of those with timely vs delayed risk-reducing bilateral salpingo-oophorectomy. A multivariable logistic regression model was used to evaluate the associations among factors related to timing of risk-reducing bilateral salpingo-oophorectomy.
RESULTS
We identified 638 BRCA1 and BRCA2 mutation carriers seen between 2012 and 2021. Of these patients, 306 (48.0%) had undergone risk-reducing bilateral salpingo-oophorectomy and 332 (52.0%) had not. When evaluating the timing of risk-reducing bilateral salpingo-oophorectomy, 136 (21.3%) underwent timely risk-reducing bilateral salpingo-oophorectomy, 239 (37.5%) had delays in risk-reducing bilateral salpingo-oophorectomy, and 263 (41.2%) had not undergone risk-reducing bilateral salpingo-oophorectomy but were younger than the National Comprehensive Cancer Network age guidelines; therefore, they were neither timely nor delayed. Patients with delay in risk-reducing bilateral salpingo-oophorectomy were significantly older at the time of genetic testing than those with timely risk-reducing bilateral salpingo-oophorectomy (mean, 49.8 vs 36.3 years; P<.001). Of the 306 patients who underwent risk-reducing bilateral salpingo-oophorectomy, those with delayed risk-reducing bilateral salpingo-oophorectomy had a significantly shorter interval between BRCA identification and risk-reducing bilateral salpingo-oophorectomy than those with timely risk-reducing bilateral salpingo-oophorectomy (median, 8.7 vs 17.6 months; P<.001). Patients with delay in risk-reducing bilateral salpingo-oophorectomy were more likely to have a personal history of cancer than those with timely risk-reducing bilateral salpingo-oophorectomy (49.8% vs 37.5%; P=.028). Of the 239 women with delay in risk-reducing bilateral salpingo-oophorectomy, 188 (78.7%) had delayed BRCA mutation identification, 29 (12.1%) had menopausal concerns, 17 (7.1%) had ongoing cancer treatment, 12 (5.0%) had coordination with breast surgery, 20 (8.4%) had miscellaneous reasons, and 19 (7.9%) had no reason documented. In the multivariate model, older age at BRCA diagnosis (odds ratio, 0.73; 95% confidence interval, 0.68-0.78; P<.001) was significantly associated with delayed risk-reducing bilateral salpingo-oophorectomy timing; those with BRCA2 mutation type were 7.54 times as likely to have timely risk-reducing bilateral salpingo-oophorectomy than BRCA1 mutation carriers (odds ratio, 7.54; 95% confidence, 3.70-16.42; P<.001).
CONCLUSION
Nearly 38% of BRCA1 and BRCA2 mutation carriers undergo or have yet to undergo risk-reducing bilateral salpingo-oophorectomy over the recommended National Comprehensive Cancer Network age. The most common reason for the delay in risk-reducing bilateral salpingo-oophorectomy was delayed identification of BRCA mutation, noted in 79% of patients with delayed risk-reducing bilateral salpingo-oophorectomy. Timely genetic testing for eligible patients can increase appropriately timed risk-reducing bilateral salpingo-oophorectomy for the prevention of ovarian cancer and reduction of mortality in BRCA mutation carriers.
背景
在携带 BRCA 突变的女性中,已证实降低风险的双侧输卵管卵巢切除术可降低妇科癌症特异性和总体死亡率。美国国家综合癌症网络建议 BRCA 突变携带者在 BRCA1 突变携带者年龄为 35 岁至 40 岁之间,BRCA2 突变携带者年龄为 40 岁至 45 岁之间,或在完成生育后进行降低风险的双侧输卵管卵巢切除术。目前,降低风险的双侧输卵管卵巢切除术的接受程度和时间以及降低风险的双侧输卵管卵巢切除术延迟的原因尚不清楚。
目的
我们旨在评估 BRCA1 和 BRCA2 突变携带者根据美国国家综合癌症网络指南接受降低风险的双侧输卵管卵巢切除术的情况,以及降低风险的双侧输卵管卵巢切除术延迟的原因。
研究设计
在这项回顾性图表审查中,我们确定了 2012 年至 2021 年期间与提供者讨论过降低风险的双侧输卵管卵巢切除术的 BRCA1 和 BRCA2 突变携带者。记录了降低风险的双侧输卵管卵巢切除术的接受情况,并根据美国国家综合癌症网络指南将患者分类为及时或延迟降低风险的双侧输卵管卵巢切除术。对于降低风险的双侧输卵管卵巢切除术延迟的患者,收集了延迟的原因。进行了比较统计分析,以评估及时与延迟降低风险的双侧输卵管卵巢切除术的患者特征。使用多变量逻辑回归模型评估与降低风险的双侧输卵管卵巢切除术时间相关的因素之间的关联。
结果
我们确定了 2012 年至 2021 年间就诊的 638 名 BRCA1 和 BRCA2 突变携带者。其中,306 名(48.0%)接受了降低风险的双侧输卵管卵巢切除术,332 名(52.0%)未接受该手术。在评估降低风险的双侧输卵管卵巢切除术的时间时,136 名(21.3%)及时接受了降低风险的双侧输卵管卵巢切除术,239 名(37.5%)有延迟,263 名(41.2%)未接受降低风险的双侧输卵管卵巢切除术,但年龄小于美国国家综合癌症网络年龄指南;因此,他们既不及时也不延迟。与及时接受降低风险的双侧输卵管卵巢切除术的患者相比,降低风险的双侧输卵管卵巢切除术延迟的患者在接受基因检测时年龄明显更大(平均年龄为 49.8 岁比 36.3 岁;P<.001)。在接受降低风险的双侧输卵管卵巢切除术的 306 名患者中,与及时接受降低风险的双侧输卵管卵巢切除术的患者相比,降低风险的双侧输卵管卵巢切除术延迟的患者接受手术的时间间隔明显缩短(中位数为 8.7 个月比 17.6 个月;P<.001)。降低风险的双侧输卵管卵巢切除术延迟的患者比及时接受降低风险的双侧输卵管卵巢切除术的患者更有可能有癌症个人史(49.8%比 37.5%;P=.028)。在 239 名降低风险的双侧输卵管卵巢切除术延迟的女性中,188 名(78.7%)延迟了 BRCA 突变的发现,29 名(12.1%)有绝经期担忧,17 名(7.1%)正在接受癌症治疗,12 名(5.0%)与乳房手术相协调,20 名(8.4%)有其他原因,19 名(7.9%)没有记录原因。在多变量模型中,BRCA 诊断时年龄较大(优势比,0.73;95%置信区间,0.68-0.78;P<.001)与降低风险的双侧输卵管卵巢切除术时间延迟显著相关;BRCA2 突变型比 BRCA1 突变携带者及时接受降低风险的双侧输卵管卵巢切除术的可能性高 7.54 倍(优势比,7.54;95%置信区间,3.70-16.42;P<.001)。
结论
近 38%的 BRCA1 和 BRCA2 突变携带者根据美国国家综合癌症网络的建议年龄接受或尚未接受降低风险的双侧输卵管卵巢切除术。降低风险的双侧输卵管卵巢切除术延迟的最常见原因是 BRCA 突变的延迟发现,在延迟降低风险的双侧输卵管卵巢切除术的患者中占 79%。对符合条件的患者进行及时的基因检测,可以增加适当时间的降低风险的双侧输卵管卵巢切除术,以预防卵巢癌并降低 BRCA 突变携带者的死亡率。