Re-prompting for ESR1 mutations in breast cancer: Improving mutation reporting and therapeutic decision-making.

559 Background: Estrogen receptor 1 mutations (ESR1m) are a significant driver of resistance to endocrine therapy in HR-positive (HRpos), HER2-negative (HER2neg) metastatic breast cancer (mBC). Identifying the presence of emergent ESR1m became relevant in late January 2023, after approval of targeted therapy. The decision support tool, Clear Value Plus (CVP), aims to improve mutation reporting by re-prompting providers to test ESR1 status upon disease progression. This aligns with the recommendation for repeat testing within the National Comprehensive Cancer Network (NCCN) Guidelines for Breast Cancer. Methods: In November 2023, CVP was modified to prompt providers to retest mBC patients on endocrine therapy for ESR1m upon progression. We retrospectively analyzed all such testing from iKnowMed, an electronic health record used by more than 2700 providers at 600 sites of care across The US Oncology Network, between November 2023 and January 2025 and analyzed changes in ESR1m status. The re-prompting mechanism was rolled out prior to the NCCN recommendation to retest in February 2024. Re-prompting was designed to provide education on the need to retest in order to identify patients appropriate for targeted therapy. Data were collected from patients with HRpos, HER2neg mBC across multiple lines of therapy. The rate of known mutation status, detected ESR1m, along with an evaluation of the ESR1m conversion rate was evaluated over 15-months. Results: There were 8,742 treatment decisions made for HRpos, HER2neg mBC; 5,903 were prior to 1 st line therapy, 1,808 prior to 2 nd line, and 1,031 beyond 2 nd line. The rate of known ESR1m status increased from 37.3% in November 2023 to 44.6% in January 2025. ESR1m were detected in 12% of decisions prior to 1 st line therapy, 19% prior to 2 nd line therapy, and 27% beyond 2 nd line. The conversion rate from unknown to known ESR1m was 9%, resulting in a potential new therapeutic option for 463 patients. The negative to positive ESR1m conversion rate was 1%, the rate of continued testing in positive patients was 9% and the rate of conversion from positive to negative was <1%. Over the testing period, the rate of mutation reporting increased with subsequent lines of therapy. Conclusions: The re-prompting strategy for ESR1m testing upon progression significantly increases mutation detection ability and coincided with an increase in reporting rate from 37.3% to 44.6%. Re-prompting enhances provider education and timely identification of mutations, enabling personalized treatment decisions using novel targeted therapies and potential improvement of patient outcomes. Rates of ESR1m detection increase with subsequent lines of therapy. ESR1m testing. Setting Mutation Detected % Mutation Not Detected % Unknown Mutation Status % TotalKnown % Total Unknown % 1st lineN=5,903 12 26 63 37 63 After 1st lineN=1,808 19 31 49 51 49 After 2nd line+N=1,031 27 40 33 67 33