School of Public Health, University of Washington, Washington, Seattle, USA.
Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Oregon, Portland, USA.
Cancer. 2022 Aug 15;128(16):3090-3098. doi: 10.1002/cncr.34349. Epub 2022 Jun 9.
Germline genetic testing enables primary cancer prevention, including through prophylactic surgery. We examined risk-reducing surgeries in unaffected individuals tested for hereditary cancer susceptibly between 2010 and 2018 in the Kaiser Permanente Northwest health system.
We used an internal genetic testing database to create a cohort of individuals who received tests including one or more high-penetrance hereditary cancer susceptibility gene. We then identified, after testing, bilateral mastectomy, bilateral salpingo-oophorectomy (BSO), and total hysterectomy procedures in electronic health record and claims data through 2019. We describe surgery utilization by genetic test results and National Comprehensive Cancer Network (NCCN) guidelines.
The cohort included 1020 individuals, 16% with pathogenic/likely pathogenic (P/LP) variants in one or more of the following genes: BRCA1, BRCA2, CHEK2, APC, MUTYH, ATM, MSH2, PALB2, BRIP1, MLH1, MSH6, EPCAM, FLCN, RAD51C, RAD51D, or TP53. Among individuals with P/LP variants making them candidates for mastectomy, BSO, or hysterectomy per NCCN guidelines, 34% (33/97), 24% (23/94), and 8% (1/12), respectively, underwent surgery during follow-up. Fifty-three percent (18/37) of hysterectomies were among APC, BRCA1, and BRCA2 P/LP variant heterozygotes, typically concurrent with BSO. Three individuals with variants of uncertain significance (only) and 22 with negative results had prophylactic surgery after genetic testing.
Uptake of risk-reducing surgery following usual care genetic testing appears to be lower than in studies that actively recruit high-risk patients and provide testing and follow-up care in specialized settings. Factors in addition to genetic test results and NCCN guidelines motivate prophylactic surgery use and deserve further study.
种系基因检测可实现癌症的一级预防，包括预防性手术。我们在 2010 年至 2018 年期间，在 Kaiser Permanente Northwest 健康系统中，对遗传性癌症易感性进行检测的无影响个体中，研究了降低风险的手术。
我们使用内部基因检测数据库创建了一个队列，其中包含接受过检测的个体，这些检测包括一种或多种高外显率遗传性癌症易感性基因。然后，我们在电子健康记录和索赔数据中，通过 2019 年确定了检测后双侧乳房切除术、双侧输卵管卵巢切除术（BSO）和全子宫切除术的手术。我们描述了根据基因检测结果和国家综合癌症网络（NCCN）指南进行的手术利用情况。
该队列包括 1020 名个体，其中 16%的个体在一个或多个以下基因中存在致病性/可能致病性（P/LP）变异：BRCA1、BRCA2、CHEK2、APC、MUTYH、ATM、MSH2、PALB2、BRIP1、MLH1、MSH6、EPCAM、FLCN、RAD51C、RAD51D 或 TP53。在根据 NCCN 指南，BRCA1、BRCA2、CHEK2、APC、MUTYH、ATM、MSH2、PALB2、BRIP1、MLH1、MSH6、EPCAM、FLCN、RAD51C、RAD51D 或 TP53 基因的 P/LP 变异使个体成为乳房切除术、BSO 或子宫切除术的候选者中，分别有 34%（33/97）、24%（23/94）和 8%（1/12）在随访期间进行了手术。53%（18/37）的子宫切除术发生在 APC、BRCA1 和 BRCA2 P/LP 变体杂合子中，通常与 BSO 同时进行。3 名个体仅存在意义不明的变异（VUS），22 名个体的检测结果为阴性，他们在基因检测后进行了预防性手术。
与积极招募高危患者并在专门环境中提供检测和随访护理的研究相比，在接受常规护理基因检测后，降低风险的手术的采用率似乎较低。除了基因检测结果和 NCCN 指南之外，还有其他因素会影响预防性手术的使用，值得进一步研究。
