University of Nevada Reno School of Medicine, Reno.
Helix, Inc, San Mateo, California.
JAMA Netw Open. 2024 Sep 3;7(9):e2435901. doi: 10.1001/jamanetworkopen.2024.35901.
Most patients with pathogenic or likely pathogenic (P/LP) variants for breast cancer have not undergone genetic testing.
To identify patients meeting family history criteria for genetic testing in the electronic health record (EHR).
DESIGN, SETTING, AND PARTICIPANTS: This study included both cross-sectional (observation date, February 1, 2024) and retrospective cohort (observation period, January 1, 2018, to February 1, 2024) analyses. Participants included patients aged 18 to 79 years enrolled in Renown Health, a large health system in Northern Nevada. Genotype was known for 38 003 patients enrolled in Healthy Nevada Project (HNP), a population genomics study.
An EHR indicating that a patient is positive for criteria according to the Seven-Question Family History Questionnaire (hereafter, FHS7 positive) assessing familial risk for hereditary breast and ovarian cancer (HBOC).
The primary outcomes were the presence of P/LP variants in the ATM, BRCA1, BRCA2, CHEK2, or PALB2 genes (cross-sectional analysis) or a diagnosis of cancer (cohort analysis). Age-adjusted cancer incidence rates per 100 000 patients per year were calculated using the 2020 US population as the standard. Hazard ratios (HRs) for cancer attributable to FHS7-positive status were estimated using cause-specific hazard models.
Among 835 727 patients, 423 393 (50.7%) were female and 29 913 (3.6%) were FHS7 positive. Among those who were FHS7 positive, 24 535 (82.0%) had no evidence of prior genetic testing for HBOC in their EHR. Being FHS7 positive was associated with increased prevalence of P/LP variants in BRCA1/BRCA2 (odds ratio [OR], 3.34; 95% CI, 2.48-4.47), CHEK2 (OR, 1.62; 95% CI, 1.05-2.43), and PALB2 (OR, 2.84; 95% CI, 1.23-6.16) among HNP female individuals, and in BRCA1/BRCA2 (OR, 3.35; 95% CI, 1.93-5.56) among HNP male individuals. Being FHS7 positive was also associated with significantly increased risk of cancer among 131 622 non-HNP female individuals (HR, 1.44; 95% CI, 1.22-1.70) but not among 114 982 non-HNP male individuals (HR, 1.11; 95% CI, 0.87-1.42). Among 1527 HNP survey respondents, 352 of 383 EHR-FHS7 positive patients (91.9%) were survey-FHS7 positive, but only 352 of 883 survey-FHS7 positive patients (39.9%) were EHR-FHS7 positive. Of the 29 913 FHS7-positive patients, 19 764 (66.1%) were identified only after parsing free-text family history comments. Socioeconomic differences were also observed between EHR-FHS7-negative and EHR-FHS7-positive patients, suggesting disparities in recording family history.
In this cross-sectional study, EHR-derived FHS7 identified thousands of patients with familial risk for breast cancer, indicating a substantial gap in genetic testing. However, limitations in EHR family history data suggested that other identification methods, such as direct-to-patient questionnaires, are required to fully address this gap.
重要性：大多数携带乳腺癌致病性或可能致病性（P/LP）变异的患者尚未接受基因检测。
目的：在电子健康记录（EHR）中识别符合基因检测家族史标准的患者。
设计、设置和参与者：本研究包括横断面（观察日期为 2024 年 2 月 1 日）和回顾性队列（观察期为 2018 年 1 月 1 日至 2024 年 2 月 1 日）分析。参与者包括在内华达州雷诺健康系统注册的年龄在 18 至 79 岁的患者。在内华达州健康项目（HNP）的一项人群基因组学研究中，已知 38003 名患者的基因型。
暴露：EHR 显示患者根据评估遗传性乳腺癌和卵巢癌（HBOC）家族风险的七问家族史问卷（简称 FHS7 阳性）符合标准。
主要结果和措施：主要结果是 ATM、BRCA1、BRCA2、CHEK2 或 PALB2 基因中存在 P/LP 变异（横断面分析）或癌症诊断（队列分析）。使用 2020 年美国人口作为标准，计算每 10 万名患者每年的年龄调整后癌症发病率。使用特定原因的危险比模型估计归因于 FHS7 阳性状态的癌症的危险比（HR）。
结果：在 835727 名患者中，423393 名（50.7%）为女性，29913 名（3.6%）为 FHS7 阳性。在 FHS7 阳性的患者中，24535 名（82.0%）在其 EHR 中没有 HBOC 遗传检测的先前证据。FHS7 阳性与 BRCA1/BRCA2（比值比 [OR]，3.34；95%置信区间 [CI]，2.48-4.47）、CHEK2（OR，1.62；95%CI，1.05-2.43）和 PALB2（OR，2.84；95%CI，1.23-6.16）中 P/LP 变异的患病率增加相关，在 HNP 女性个体中，BRCA1/BRCA2（OR，3.35；95%CI，1.93-5.56），在 HNP 男性个体中。在 131622 名非 HNP 女性个体中，FHS7 阳性也与显著增加的癌症风险相关（HR，1.44；95%CI，1.22-1.70），但在 114982 名非 HNP 男性个体中无显著相关性（HR，1.11；95%CI，0.87-1.42）。在 1527 名 HNP 调查受访者中，383 名 EHR-FHS7 阳性患者中的 352 名（91.9%）为调查-FHS7 阳性，但 883 名调查-FHS7 阳性患者中仅有 352 名（39.9%）为 EHR-FHS7 阳性。在 29913 名 FHS7 阳性患者中，仅在解析自由文本家族史评论后才确定了 19764 名（66.1%）患者。EHR-FHS7 阴性和 EHR-FHS7 阳性患者之间也观察到社会经济差异，表明在记录家族史方面存在差异。
结论和相关性：在这项横断面研究中，EHR 衍生的 FHS7 确定了数千名具有乳腺癌家族风险的患者，表明基因检测存在巨大差距。然而，EHR 家族史数据的局限性表明，需要其他识别方法，例如直接向患者发送问卷，以充分解决这一差距。
