Abstract PS1-11-26: Esr1 mutations and use of the oral serd elacestrant in metastatic breast cancer patients in austria: results from the agmt_mbc-registry

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Abstract Background: Elacestrant is the first oral Selective Estrogen Receptor Degrader (SERD) to be approved in the EU as of September 2023. Since its approval, testing for mutations in the estrogen receptor 1 (ESR1) gene has become standard care for patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC) in low- to intermediate risk disease. ESR1 mutations are a known mechanism of resistance to aromatase inhibitors (AIs), with their frequency significantly increasing after AI treatment. This study presents the first real-world data from the Austrian Study Group of Medical Tumor Therapy (AGMT) MBC Registry regarding ESR1 testing and elacestrant use. Patients and Methods: The AGMT MBC Registry is a nationwide, multicenter, ongoing retrospective and prospective registry for MBC patients in Austria. For this analysis, only patients with sufficient data quality were included. ESR1 mutation testing was performed using various techniques and test kits, following local practices. Results: As of March 11, 2025, the registry included 3,094 patients, of whom 2,956 were evaluable. Among these, 132 patients (4.5%) had documented ESR1 testing. A total of 59 tests were performed on 54 patients after the approval of elacestrant: 33 (55.9%) via liquid biopsy and 26 (44.1%) via tissue analysis; three tests in three patients had no or inconclusive results. The majority of patients had HR+/HER2- disease (n=48; 92.3%). A total of 14 patients (27.5%) had a positive ESR1 result (30.4% of all tests). Six distinct ESR1 mutations were identified: D538G, E380Q, Y537S, Y537N, M396V, and L536_D538>P. Notably, three patients (5.5%) had multiple ESR1 mutations. These combinations were: E380Q/Y537S/M396V, D538G/E380Q, and D538G/Y537N. Of the 14 patients with positive ESR1 test results, 7 patients (50.0%) initiated elacestrant treatment between the first and eleventh line of therapy, with five patients continuing treatment at the data cut-off. Updated outcome data will be presented at the meeting.Eleven, 8 and 9 patients with ESR1 mutations (n=14) had additional testing for PIK3CA, TP53 and for BRCA1/2, respectively. In 7 patients co-mutations in PIK3CA were found. Four of these patients were treated with a PI3-kinase inhibitor, and one received elacestrant in combination with alpelisib. Co-mutations with TP53 and BRCA2 were found in 3 and 1 patient, respectively. Conclusion: This real-world data highlights the clinical relevance of ESR1 mutations in HR+/HER2- metastatic breast cancer patients and underscores the potential impact of molecular-guided treatment. The association of ESR1 mutations with co-mutations in PIK3CA, TP53, and BRCA2 suggests the need for personalized treatment approaches. Further follow-up and outcome data will provide more insights into the long-term efficacy of elacestrant in this cohort. Citation Format: S. P. Gampenrieder, G. Rinnerthaler, A. Pichler, W. Herz, R. Pusch, C. Dormann, C. Suppan, M. Sandholzer, T. Winder, S. Heibl, L. Scagnetti, C. Schmitt, A. F. Zabernigg, D. Egle, C. Hager, P. Pichler, F. Roitner, J. Andel, K. Strasser-Weippl, R. Bartsch, V. Castagnaviz, M. Hubalek, M. Knauer, C. F. Singer, R. Greil. Esr1 mutations and use of the oral serd elacestrant in metastatic breast cancer patients in austria: results from the agmt_mbc-registry [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 PS1-11-26.

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