Mortimer Joanne E, Lindsey Sidney S, Zukin Elyssa, Park Wai, Sturgeon Duveen, Solomon Ilana, Blazer Kathleen, Gray Stacy W, Bonner Joseph D, Gruber Stephen B
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California.
Center for Precision Medicine, City of Hope National Medical Center and Beckman Research Institute, Duarte, California.
JAMA Netw Open. 2025 Sep 2;8(9):e2531577. doi: 10.1001/jamanetworkopen.2025.31577.
Barriers to germline testing make it difficult to determine the prevalence of pathogenic or likely pathogenic (P/LP) variants in BRCA1 and BRCA2 in underrepresented populations.
To determine P/LP variants in BRCA1 and BRCA2 in women with breast cancer enrolled in the Implementing Next-Generation Sequencing for Precision Intervention and Risk Evaluation (INSPIRE) study.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients from City of Hope Duarte, California, and Upland, California, with a breast cancer diagnosis of any stage (0 to IV) from July 2020 to October 2023 who were enrolled in the INSPIRE biorepository study. Blood, buccal smears, or saliva were collected for germline testing of 155 genes. Data were analyzed from October 2023 to December 2024.
Women with breast cancer, including underrepresented populations, received germline testing to determine P/LP variants in BRCA1 and BRCA2 genes.
The main outcome was prevalence of P/LP variants in BRCA1 and BRCA2 in women with breast cancer.
A total of 2401 women with breast cancer underwent germline testing, including 136 African American or Black (5.7%), 365 Asian (15.2%), 15 American Indian or Alaska Native women (0.5%), 8 Native Hawaiian or Other Pacific Islander women (0.3%), and 1666 White (69.4%), 86 Other (3.6%), and 125 unknown (5.2%). Ethnicity was reported for 737 Hispanic or Latina women (30.7%) and 1545 non-Hispanic women (64.3%). P/LP variants in BRCA1 or BRCA2 were identified in 16 Asian women (4.4%), 11 African American or Black women (8.1%), and 80 White women (4.8%). Hispanic women with breast cancer were 2.58 times as likely as non-Hispanic women to carry a P/LP germline variant in BRCA1 than BRCA2 variants (odds ratio [OR], 2.58 [95% CI, 1.16-5.88]; P = .02). P/LP variants in BRCA1 were more likely to be identified in Hispanic women (22 of 737 [3.0%]) than in non-Hispanic women (25 of 1545 [1.6%]) (OR, 1.87; [95% CI, 1.04-3.34]; P = .02). Additionally, 16 of 116 women older than age 60 years (13.7%) were also found to have P/LP variants.
This large cohort study of women with breast cancer who underwent germline testing provided information about BRCA1 and BRCA2 in a population enriched for Hispanic women and reported the prevalence of P/LP variants when universal BRCA1 and BRCA2 testing is offered to women with breast cancer.
生殖系检测的障碍使得难以确定在代表性不足的人群中，BRCA1和BRCA2基因中致病或可能致病（P/LP）变异的患病率。
确定参与精准干预与风险评估的下一代测序实施（INSPIRE）研究的乳腺癌女性中BRCA1和BRCA2基因的P/LP变异。
设计、背景和参与者：这项队列研究纳入了来自加利福尼亚州杜阿尔特市希望之城和加利福尼亚州高地市，在2020年7月至2023年10月期间被诊断为任何阶段（0至IV期）乳腺癌且参加了INSPIRE生物样本库研究的患者。收集血液、口腔涂片或唾液用于155个基因的生殖系检测。数据于2023年10月至2024年12月进行分析。
患有乳腺癌的女性，包括代表性不足的人群，接受生殖系检测以确定BRCA1和BRCA2基因中的P/LP变异。
主要结局是乳腺癌女性中BRCA1和BRCA2基因P/LP变异的患病率。
共有2401名乳腺癌女性接受了生殖系检测，其中包括136名非裔美国人或黑人（5.7%）、365名亚洲人（15.2%）、15名美洲印第安人或阿拉斯加原住民女性（0.5%）、8名夏威夷原住民或其他太平洋岛民女性（0.3%）、1666名白人（69.4%）、86名其他种族（3.6%）以及125名身份不明者（5.2%）。报告了737名西班牙裔或拉丁裔女性（30.7%）和1545名非西班牙裔女性（64.3%）的种族信息。在16名亚洲女性（4.4%）中、11名非裔美国人或黑人女性（8.1%）中以及80名白人女性（4.8%）中发现了BRCA1或BRCA2基因的P/LP变异。患有乳腺癌的西班牙裔女性携带BRCA1基因P/LP生殖系变异的可能性是非西班牙裔女性携带BRCA2基因变异可能性的2.58倍（优势比[OR]，2.58[95%置信区间，1.16 - 5.88]；P = 0.02）。在西班牙裔女性（737名中的22名[3.0%]）中比在非西班牙裔女性（1545名中的25名[1.6%]）中更有可能发现BRCA1基因的P/LP变异（OR，1.87；[95%置信区间，1.04 - 3.34]；P = 0.02）。此外，在116名年龄大于60岁的女性中，有16名（13.7%）也被发现携带P/LP变异。
这项对接受生殖系检测的乳腺癌女性进行的大型队列研究，提供了关于富含西班牙裔女性人群中BRCA1和BRCA2基因的信息，并报告了在为乳腺癌女性提供BRCA1和BRCA2普遍检测时P/LP变异的患病率。
