Abstract PS3-10-01: Impact of ER Reduction Rate on Survival Outcomes in ER-Positive/HER2-Negative Breast Cancer Post-Neoadjuvant Chemotherapy

Abstract Background: The conversion of estrogen receptor (ER)-positive to ER-negative status after neoadjuvant chemotherapy (NAC) is often considered a poor prognostic indicator in ER-positive/HER2-negative breast cancer (BC). However, the prognostic impact of the extent of ER reduction remains unclear. Methods: This study included ER-positive/HER2-negative BC patients without pathological complete response after NAC. Cox regression assessed the relationship between ER reduction rate (ERr) and invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival (OS). Time-dependent receiver operating characteristic curves (ROC) and concordance index compared model discrimination. Results: A total of 519 patients were followed up for a median of 81 months. Participants were categorized into two groups based on the restricted cubic spline analysis, using a cut-off value of 10%. A total of 415 patients (79.96%) had ERr 10%, while 104 patients (20.04%) had ERr ≥ 10%. In the multivariate Cox regression model, participants with ERr ≥ 10% had a significantly higher risk of iDFS (hazard ratio HR, 2.405; 95% confidence interval CI, 1.703–3.395), DDFS (HR, 2.278; 95% CI, 1.575–3.294), and OS (HR, 2.224; 95% CI, 1.450–3.411) compared to those with ERr 10%. Multiple sensitivity analyses yielded consistent results. Based on time-dependent ROC, adding the ERr to the prognostic model significantly improved predictions of iDFS (p = 0.025) and DDFS (p = 0.044). Conclusions: ERr ≥ 10% is associated with poorer outcomes in ER-positive/HER2-negative BC patients treated with NAC, highlighting the need for novel therapeutic strategies for this population. Citation Format: S. Liu, Y. Qiu, Y. Wang, W. Cai, H. Peng, Q. Cai, L. Wu, J. Li, L. Yu, M. Chen, L. Chen, C. Wang, F. Fu. Impact of ER Reduction Rate on Survival Outcomes in ER-Positive/HER2-Negative Breast Cancer Post-Neoadjuvant Chemotherapy 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 PS3-10-01.