Abstract
IMPORTANCE: 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. OBJECTIVE: 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. EXPOSURES: Women with breast cancer, including underrepresented populations, received germline testing to determine P/LP variants in BRCA1 and BRCA2 genes. MAIN OUTCOMES AND MEASURES: The main outcome was prevalence of P/LP variants in BRCA1 and BRCA2 in women with breast cancer. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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.