Abstract Background Targeted therapies have transformed treatment for HR+/HER2- metastatic breast cancer (mBC), but optimal use depends on timely biomarker testing and matched therapy selection. This study evaluated national trends in PIK3CA, PTEN, AKT1 and ESR1 biomarker testing and treatment patterns among U.S. patients (pts) in community oncology clinics and examined factors associated with timely biomarker testing. Methods We conducted a retrospective cohort study of adult pts (≥18 years) with HR+/HER2- mBC treated between 01/01/2018 and 01/31/2025, using de-identified, electronic health record-derived data from the United States Flatiron Health Network. Eligible pts received at least one line of therapy at U.S. community oncology practices. Biomarker testing and treatment patterns across the first three lines of therapy (1L-3L) were analyzed descriptively. Logistic regression model evaluated associations between timely testing and baseline demographic, socioeconomic (SES), and clinical characteristics. Timely testing was defined as completing biomarker testing with results available before initiating a line of therapy for which an approved targeted treatment was available. Results Among 6,197 eligible pts who received 1L therapy, 3,550 progressed to 2L and 2,045 to 3L during the study period. Biomarker testing rates increased over time prior to 1L (from 4% in 2018 to 35% in 2024), 2L (from 9% to 69%), and 3L (from 13% to 83%). CDK4/6 inhibitors were the predominant 1L treatment regardless of biomarker status. In 2L and 3L, treatment patterns became more fragmented. Among pts with known PIK3CA mutations, the use of targeted approved therapies was 32% in 2L and 36% in 3L in 2019, compared to 27% and 29% in 2024. Among pts with ESR1+, elacestrant use rose from 22% in 2023 to 29% in 2024 in 2L and remained steady at 26-27% in 3L. In AKT1/PTEN+ pts, capivasertib use was 6% in 2L and 11% in 3L in 2024. Among pts with no test, or with negative or inconclusive biomarker results, 1% in 1L, 9% in 2L and 17% in 3L received Antibody Drug Conjugates in 2024. Treatment choices for dual-mutant (ESR1+ with either PIK3CA, AKT1 or PTEN) pts remained highly variable, with no dominant regimen: 27% received targeted therapies in 2L versus 34% in 3L. Pts were less likely to receive timely biomarker testing if they were older, lived in lower-SES areas, were treated at smaller practices, or had a worse ECOG score. However, timely testing became more common in more recent years. Conclusions Despite the availability of targeted therapies, major gaps persist in both biomarker testing and the uptake of these treatments. In 2024, nearly one-third of pts remained untested before 2L, and only 35% were tested prior to initiating 1L, limiting timely access to newly approved options. Even when actionable mutations were identified, over two-thirds of eligible pts did not receive matched therapies. Timely testing was less common in smaller practices and lower-SES settings, highlighting systemic barriers to precision oncology. To close these gaps, coordinated, equity-focused strategies are needed to improve timely testing and ensure appropriate use of targeted treatments across all pts populations. Study Number: SL46196 and PL-03044. Financial Statement: This study was sponsored by Genentech, Inc., a member of the Roche Group. Citation Format: I. M. Abbass, D. Lebovitch, N. Jain, T. Stricker, S. Nunnery, A. Pregenzer, E. Behan, R. Wang, L. Chen, P. Dhillon, Y. Liu, T. Szado, E. Yu, S. Ogale. Trends and Barriers in Biomarker Testing and Treatment Patterns in HR+/HER2- Metastatic Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-12-27.
Abbass et al. (Tue,) studied this question.