Abstract PS1-12-08: Real-world ESR1 mutation (ESR1m) testing and positivity rates in patients with ER+, HER2- metastatic breast cancer (MBC)

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Abstract Background: As the MBC treatment landscape evolves, understanding ESR1m testing patterns for ER+, HER2- MBC is essential to identify patients for targeted therapies. Despite existing guidelines recommending testing of patients with MBC at progression for ESR1m, real-world data on testing and mutation rates are limited. Therefore, we described ESR1m testing and positivity (+) rates in patients with ER+, HER2- MBC to identify opportunities for improved ESR1m test utilization. Methods: This retrospective, observational study included patients aged ≥18 years at ER+, HER2- MBC diagnosis (Dx) who initiated 1st line (1L) therapy with aromatase inhibitors (AI) or selective estrogen receptor degraders (SERDs) ± CDK4/6 inhibitors (CDK4/6i) from 1/1/20-3/31/25. Flatiron Health Research Database (FHRD), a de-identified US-based electronic health record database, was used to estimate ESR1m+ rates in windows defined as: A) initial early breast cancer (EBC) Dx date or 90 days before de novo MBC Dx to last patient contact, B) MBC Dx date to 1L initiation date+28 days, C) during line of therapy (LoT;start to end date), and D) at LoT initiation (90 days before to 28 days after LoT initiation). Results: Of all 12148 patients, 48% (n=5874) had ≥1 ESR1m test and most tested patients (n=3650/5874; 62%) were tested only once (mean:1.6 test/patient). Among all patients, testing rates were similar at each LoT initiation (25-29%). In exploratory analyses of all patients, post-2023 testing rates were often higher than pre-2023, especially at 1L (34 vs 20%) and 2L initiation (36 vs 26%). When considering patients with data available on ESR1m testing by sample type (n=2028), ∼60% were in tissue only and ∼40% were in blood only. Among a subgroup of patients with de novo MBC who received 1L AI±CDK4/6i, testing rates at 2L and 3L initiation were 27-28%. For the subgroup of patients with EBC who relapsed and developed MBC while on adjuvant AI±CDK4/6i or ≤12 months after completion, the testing rate was the highest during 1L (38%). Among all patients, ESR1m+ was 15% during 1L and increased to 37% at 3L initiation. Among patients with de novo MBC (received 1L AI±CDK4/6i), ESR1m+ was highest at 3L initiation (40%). Among the relapsed patients, ESR1m+ was 23% at 1L initiation, 31% at 2L initiation, and 33% at 3L initiation. Conclusion: Among all patients with MBC, 52% were never tested and only 34-36% were tested at 1L and 2L initiation from 2023 onward. Importantly, lower rates of ESR1m+ were observed in the real-world compared to clinical trials. This may be due to suboptimal test timing, poor patient identification for testing, and frequent use of tissue-based testing, which is less sensitive than the recommended blood-based ctDNA used in clinical trials. These results highlight an unmet need for increased ESR1m testing using blood-based ctDNA to optimize patient identification for targeted therapies in ER+, HER2- MBC. Citation Format: C. Liao, N. Bansal, J. John, M. Bhave, F. Bidard, T. Marquart, A. Chawla, L. Williams. Real-world ESR1 mutation (ESR1m) testing and positivity rates in patients with ER+, HER2- metastatic breast cancer (MBC) [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 PS1-12-08.

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