Abstract PS1-12-19: Disease natural history and care quality assessment of hormone receptor positive / human epidermal growth factor receptor 2 negative metastatic breast cancer (HR+/HER2- mBC) - an international multicentric study

Abstract Background Despite early detection and treatment, ∼30% of early-stage HR+ HER2− breast cancer (BC) patients relapse. Rebiopsy at recurrence is recommended by international guidelines when feasible, as it informs optimal treatment selection. Molecular profiling of metastatic sites is essential to reassess HER2 status and detect actionable genomic alterations such as BRCA1/2, PIK3CA, and AKT1, guiding sequencing of therapies in the metastatic setting. The DIGICORE consortium enables detailed cancer phenotyping and quality of care assessment through automated near real-time data extraction. Here, we report real-world data from HR+ HER2- mBC patients treated at five European DIGICORE centres. Methods Cohorts of HR+ (ER ≥ 10%) HER2- mBC diagnosed between 2018 and 2023 were identified at each centre. Clinical data structured to the OMOP common data model and aligned to key oncological variables in the Minimal Essential Description of Cancer framework (DIGICORE) were automatically extracted. Data were analysed using the Vantage6 federation platform (IKNL, Netherlands) via Medical Data Works (Netherlands). Subcohorts were defined by disease history (de novo vs recurrent mBC) and HER2 status (HER2-low vs HER2-zero). Only anonymous, aggregate results were shared across centres, preserving privacy. Results A total of 1175 HR+HER2- mBC patients were identified. Due to ongoing curation, analyses focus on 529 patients with deep phenotypic data. Of these patients, 33.3% were de novo metastatic (60.2% HER2-low, 33.0% HER2-zero, and 6.8% undetailed HER2-) and 66.7% were a relapse of a previous early-stage BC (62.9% HER2-low, 36.0% HER2-zero, and 1.1% undetailed HER2-). Of the latter, 78.5% of patients were rebiopsied at relapse, of which 8.1% were HER2-positive at the early stage.Amongst patients who underwent genomic testing, 16.1% carried a germline BRCA1 or BRCA2 mutation, while 50%, 4.2%, and 4.2% carried a somatic PIK3CA, AKT1 or ERBB2 mutation, respectively. Among 320 patients with known metastatic sites, 32.5% had bone-only and 67.5% visceral metastases. Conclusions This federated network enables real-world analysis of phenotypic, genotypic, and care variables for patients with HR+ HER2- mBC. Improvement of data capture and curation, as well as addition of treatment patterns to the analysis, is ongoing. Notably, 8.1% of HER2- mBC are a relapse of HER2+ early BC, highlighting the need for rebiopsy. More than half of patients could benefit from therapy targeting an actionable gene mutation. Citation Format: S. Theophanous, L. Revie, O. Bouissou, F. Duhoux, P. Galgane Banduge, A. Choudhury, A. Collard, W. Hai Deng, G. Hall, R. Foppen, V. Gouthamchand, I. Kaczmarczyk, E. Krasniqi, L. Licata, A. Lobo Gomes, L. Sanchez Gomez, A. van Maanen, G. Podevijn, E. Ross, J. Thonnard, A. Thomas, C. Twelves, X. Fernandez, C. Van Marcke. Disease natural history and care quality assessment of hormone receptor positive / human epidermal growth factor receptor 2 negative metastatic breast cancer (HR+/HER2- mBC) - an international multicentric study 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 PS1-12-19.