Real-world treatment patterns and clinical outcomes in patients with emerging estrogen receptor 1 (ESR1)-mutated ER+ metastatic breast cancer in the U.S., 2018-2024.

PURPOSE: Clinical studies have highlighted the potential utility of monitoring for Estrogen receptor alpha 1 (ESR1) mutation (m) (ESR1m) emergence during first-line therapy (1L) for metastatic breast cancer (mBC). However, less is known about the real-world practice for patients with emergent ESR1m before progression and their outcomes. This study aimed to characterize real-world treatment patterns among patients with mBC who underwent ESR1m mutation testing during first-line (1L) therapy, and to evaluate the association between ESR1m detection during 1L and clinical outcomes. METHODS: This retrospective, observational cohort study used the US-based, deidentified Flatiron Health Research Database and included patients diagnosed with ER+/human epidermal growth factor receptor 2-negative (HER2-) metastatic BC between 2018 and June 2024. rwOS and rwPFS were estimated using the Kaplan-Meier methodology and compared after propensity score matching. Clinical outcomes were evaluated from the time of first ESR1 test during 1L therapy to minimize time-related bias. RESULTS: 7772 patients who initiated 1L therapy were included. Treatment patterns in 1L were comparable between patients with (n = 240) and without (n = 1095) ESR1m detected during 1L. Among patients tested for ESR1m mutations during 1L, detection of ESR1m was associated with significantly shorter rwPFS and OS from the time of testing, both before and after propensity score matching (rwPFS hazard ratio [HR] 0.68 [95%CI: 0.48-0.96], rwOS HR: 0.58 [95%CI: 0.36-0.95]). CONCLUSIONS: Detection of ESR1m during 1L was associated with poorer clinical outcomes. These findings highlight the clinical relevance of ESR1m emergence prior to progression and underscore the need for strategies to better identify and manage patients with emerging endocrine resistance. CLINICAL TRIAL: Not applicable.