Abstract PS5-03-16: Clinical Outcomes of ER-Positive to Negative Conversion Versus TNBC: Evidence from an18F-FES PET/CT Guided Propensity-Score-Matched Study

Abstract Background: Patients with estrogen receptor (ER)-positive breast cancer may experience ER-negative conversion (ER loss) during disease progression. 18F-fluoroestradiol positron emission tomography/computed tomography (18F-FES PET/CT) offers a practical approach for comprehensive ER evaluation across all metastatic sites, allowing early identification of ER conversion—especially valuable for cases where biopsy is technically challenging. This study aimed to compare survival outcomes and clinical characteristics between ER loss and metastatic triple-negative breast cancer (mTNBC) patients, exploring the prognostic implications of dynamic ER changes. Methods: This retrospective study screened 808 patients with ER-positive, HER2-negative breast cancer at initial diagnosis who underwent 18F-FES PET/CT after diagnosis of recurrent or metastatic disease from 2017 to 2023 at Fudan University Shanghai Cancer Center. Among them, 82 patients with functional ER loss detected by FES-PET at metastatic sites before first-line treatment were identified. 115 contemporaneous standard mTNBC patients with complete medical records were enrolled in control group. Propensity score matching (PSM) was used to balance baseline characteristics (number of metastatic sites, visceral/liver/lung/bone metastasis, taxane therapy history; caliper = 0.1). Results: PSM matched 59 patients per group and baseline clinical characteristics are well-balanced. FES-PET showed 71.7% concordance with IHC. Median progression-free survival (PFS) was significantly shorter in ER loss group compared with mTNBC (6.7 vs 12.0 months, HR=1.55, P=0.042). Objective response rate (ORR) (15.3% vs 37.3%) and disease control rate (DCR) (72.9% vs 84.7%, P=0.044) favored mTNBC, as well. Androgen receptor (AR) expression is available in 25 and 32 patients in ER loss and mTNBC group, respectively, and AR pathway positivity (≥10%) was significantly higher in ER loss group (88.0% vs 25.0%, P<0.0001). 28 of 59 (47.5%) ER loss patients received chemotherapy, and 18 of them received capecitabine based first-line therapy, while 34 of 59 (57.6%) mTNBC patients received platinum-based chemotherapy and 8 of 59 mTNBC patients had PD-1/PD-L1 exposure in first-line therapy. Conclusions: Our study reveals that patients with functional ER loss defined by FES-PET exhibit worse outcomes than mTNBC, potentially attributed to lighter treatment intensity and AR pathway activation. These findings suggest that functional ER-negative conversion, detectable via whole-body FES PET/CT, may identify a distinct high risk subgroup requiring TNBC-level treatment intensification. Future studies should investigate underlying mechanisms and evaluate AR-targeted therapies in this population. Citation Format: B. Wang, M. Li, Y. Xie, Z. Yang. Clinical Outcomes of ER-Positive to Negative Conversion Versus TNBC: Evidence from an18F-FES PET/CT Guided Propensity-Score-Matched 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 PS5-03-16.