Department of Medicine, Stanford University, Stanford, California.
Department of Epidemiology and Population Health, Stanford University, Stanford, California.
JAMA Oncol. 2020 Apr 1;6(4):e196400. doi: 10.1001/jamaoncol.2019.6400. Epub 2020 Apr 9.
The increasing use of germline genetic testing may have unintended consequences on treatment. Little is known about how women with pathogenic variants in cancer susceptibility genes are treated for breast cancer.
To determine the association of germline genetic testing results with locoregional and systemic therapy use in women diagnosed with breast cancer.
DESIGN, SETTING, AND PARTICIPANTS: For this population-based cohort study, data from women aged 20 years or older who were diagnosed with stages 0 to III breast cancer between 2014 and 2016 were accrued from the Surveillance, Epidemiology and End Results (SEER) registries of Georgia and California. The women underwent genetic testing within 3 months after diagnosis and were reported to the Georgia and California SEER registries by December 1, 2017.
Pathogenic variant status based on linked results of clinical germline genetic testing by 4 laboratories that did most such testing in the studied regions.
Potential deviation of treatment from practice guidelines was assessed in the following clinical scenarios: (1) surgery: receipt of bilateral mastectomy by women eligible for less extensive unilateral surgery (unilateral breast tumor); (2) radiotherapy: omission in women indicated for postlumpectomy radiotherapy (all lumpectomy recipients except age ≥70 with stage I, estrogen and/or progesterone receptor [ER/PR] positive, ERBB2 [formerly HER2]-negative disease); and (3) chemotherapy: receipt by women eligible to consider chemotherapy omission (stages I-II, ER/PR-positive, ERBB2-negative, and 21-gene recurrence score of 0-30, which was the upper limit of the intermediate risk range during the study years). The adjusted percentage treated and adjusted odds ratio (OR) are reported based on multivariable modeling for each treatment-eligible group.
A total of 20 568 women (17.3%) of 119 198 were eligible (mean [SD] age, 51.4 [12.2]). Compared with women whose test results were negative, those with BRCA1/2 pathogenic variants were more likely to receive bilateral mastectomy for a unilateral tumor (61.7% vs 24.3%; OR, 5.52, 95% CI, 4.73-6.44), less likely to receive postlumpectomy radiotherapy (50.2% vs 81.5%; OR, 0.22, 95% CI, 0.15-0.32), and more likely to receive chemotherapy for early-stage, ER/PR-positive disease (38.0% vs 30.3%; OR, 1.76, 95% CI, 1.31-2.34). Similar patterns were seen with pathogenic variants in other breast cancer-associated genes (ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, and TP53) but not with variants of uncertain significance.
Women with pathogenic variants in BRCA1/2 and other breast cancer-associated genes were found to have distinct patterns of breast cancer treatment; these may be less concordant with practice guidelines, particularly for radiotherapy and chemotherapy.
种系基因检测的使用日益增加，可能会对治疗产生意想不到的后果。关于携带癌症易感性基因种系变异的女性如何接受乳腺癌治疗，人们知之甚少。
确定种系基因检测结果与女性乳腺癌患者接受局部区域和全身治疗之间的关联。
设计、设置和参与者：在这项基于人群的队列研究中，数据来自于 2014 年至 2016 年间在佐治亚州和加利福尼亚州的监测、流行病学和最终结果（SEER）登记处诊断为 0 期至 3 期乳腺癌的 20 岁或以上的女性。这些女性在诊断后 3 个月内接受了基因检测，并于 2017 年 12 月 1 日前向佐治亚州和加利福尼亚州 SEER 登记处报告。
根据在研究地区进行大部分此类检测的 4 家临床种系基因检测实验室的连锁检测结果确定致病性变异状态。
在以下临床情况下评估治疗与实践指南的潜在偏差：（1）手术：符合单侧手术（单侧乳房肿瘤）适应证的女性接受双侧乳房切除术；（2）放疗：符合接受保乳术后放疗适应证的女性（除年龄≥70 岁、I 期、雌激素和/或孕激素受体[ER/PR]阳性、ERBB2[以前称为 HER2]阴性疾病外的所有保乳术接受者）；（3）化疗：符合考虑化疗豁免条件的女性（I-II 期、ER/PR 阳性、ERBB2 阴性、21 基因复发评分 0-30，这是研究期间中危范围的上限）。根据多变量模型，为每个有治疗资格的组报告接受治疗的调整后百分比和调整后的优势比（OR）。
在 119198 名女性中，共有 20568 名（17.3%）符合条件（平均[SD]年龄为 51.4[12.2]岁）。与检测结果为阴性的女性相比，BRCA1/2 致病性变异的女性更有可能接受单侧肿瘤的双侧乳房切除术（61.7%比 24.3%；OR，5.52，95%CI，4.73-6.44），不太可能接受保乳术后放疗（50.2%比 81.5%；OR，0.22，95%CI，0.15-0.32），更有可能接受早期 ER/PR 阳性疾病的化疗（38.0%比 30.3%；OR，1.76，95%CI，1.31-2.34）。其他乳腺癌相关基因（ATM、CDH1、CHEK2、NBN、NF1、PALB2、PTEN 和 TP53）的致病性变异也出现了类似的模式，但不确定意义的变异则没有。
携带 BRCA1/2 和其他乳腺癌相关基因的致病性变异的女性发现其乳腺癌治疗模式存在明显差异；这些差异可能与治疗指南不一致，特别是在放疗和化疗方面。
