Racial Differences in ctDNA Profiles, Targeted Therapy Use, and Outcomes in Metastatic Breast Cancer.

Importance: Black patients with metastatic breast cancer (mBC) have higher mortality rates than White patients despite advances in treatment. Objectives: To examine whether Black patients with metastatic breast cancer have different genomic profiles compared with White patients and whether there are inequities in targeted treatment use between these groups. Design, Setting, and Participants: This retrospective, population-based cohort study assessed adult patients with mBC who underwent genomic profiling at academic institutions in the US between January 1, 2015, and December 31, 2023. Data analysis was performed between July 2023 and July 2024. A validation cohort was also included. Exposures: Targeted treatment use. Main Outcomes and Measures: The main outcomes were differences in circulating tumor DNA profiles and use of phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors between Black and White patients with metastatic breast cancer. Results: The study sample included 1327 women with mBC (mean [SD] age, 58.0 [12.8] years; 140 Black and 1057 White). Black patients had a significantly higher rate of GATA3 single-nucleotide variants (odds ratio, 2.31; 95% CI, 1.17-4.54; P = .02) and CCND2 copy number variants (odds ratio, 4.63; 95% CI, 1.79-11.97; P = .002) on multivariate analysis. These differences were validated in a population-based evidence cohort of 27 224 patients. Black patients with PIK3CA single-nucleotide variants were significantly less likely to receive PI3K inhibitors than White patients (1 of 17 [5.9%] vs 45 of 156 [28.8%]; P = .04), whereas there was no difference in use of CDK4/6 and mTOR inhibitors, which do not require a targetable alteration. Black patients had a shorter overall survival from the time of circulating tumor DNA testing compared with White patients. Conclusions and Relevance: This cohort study of patients with mBC found somatic differences, shorter overall survival, and targeted treatment disparities in PI3K inhibitor use in Black compared with White patients despite equal incidence of PIK3CA alterations. Researchers should consider these differences when designing future research and interventions to address the striking and persistent outcomes gap between Black and White patients with mBC.