Abstract Background: In a previous cohort study analysis on 503 patients with node-positive early breast cancer (eBC) who remained premenopausal after 5 years of LHRHa treatment, we showed that the extension of endocrine therapy (ET) either with tamoxifen alone or by continuing previous LHRHa was associated with reduced invasive and distant breast cancer recurrences (Valenza, ASCO 2025). Due to the relative higher incidence of long-term recurrences in patients with luminal A-like eBC, the benefit of eET may differ according to surrogate breast cancer subtypes. Methods: We conducted a cohort study on two ongoing prospective datasets (Young Women's Study and European Institute of Oncology's Breast Cancer Dataset) to evaluate the clinical benefit of eET in women who had completed 5 years of adjuvant LHRHa, remained premenopausal and had no evidence of distant or locoregional recurrence. This study included women 40y at diagnosis (from 2005-2016) with node-positive HR+ eBC, with ductal, lobular, or ductolobular histotype, receiving or not eET (tamoxifen monotherapy or LHRHa+tamoxifen/aromatase inhibitor AI). Endpoints included invasive breast cancer-free survival (IBCFS) and distant recurrence-free survival (DRFS) calculated from the 6th year of ET (study baseline) and assessed with the propensity score (PS) weighted analysis. We performed a subgroup analysis according to the following surrogate breast cancer subtypes: luminal A-like (i.e., Ki6720%, and progesterone receptor (PgR)≥20%, and Grade 1/2, and HER2-negative), luminal B-like/HER2-negative (i.e., Ki67≥20%, or PgR20%, or Grade 3; and HER2-negative), and HER2-positive (i.e., HER2 positive per ASCO/CAP). Results: 487 patients were included (see Table): 276 received eET for a median duration of 3.7 years (IQR: 2.2-5.0). Overall, 89 (18.3%), 298 (61.2%) and 100 (20.5%) had a luminal A-like, luminal B-like and HER2-positive disease. At a median follow-up of 7.3 years (from the study baseline), the PS weighted Hazard Ratio (HR) for IBCFS comparing the eET to the non-eET group was 0.64 (95% CI, 0.45-0.91) in all patients, and 0.68 (95% CI, 0.34-1.40) in luminal A-like, 0.63 (95% CI, 0.41-0.98) in luminal B-like, and 0.62 (95% CI, 0.22-1.78) in HER2-positive subgroup. The PS weighted cause-specific HR for DRFS was 0.50 (95% CI, 0.32-0.79) in all patients, and 0.34 (95% CI, 0.12-0.92) in luminal A-like, 0.53 (95% CI, 0.31-0.92) in luminal B-like, and 0.77 (95% CI, 0.18-3.22) in HER2-positive subgroup. Conclusion: In this subanalysis, the benefit of eET was observed across all surrogate breast cancer subtypes. Notably, the magnitude of clinical benefit in terms of DRFS appeared greater in patients with a luminal A-like eBC, a finding that warrants confirmation in larger, prospective cohorts. Citation Format: C. Valenza, Y. Zheng, M. Milano, D. Trapani, E. Giordano, L. Guidi, P. Berton Giachetti, L. Boldrini, G. Castellano, J. Katrini, B. Malagutti, G. Antonarelli, F. Conforti, G. J. Kirkner, C. Sangalli, D. E. Kate, M. Colleoni, M. M. Regan, E. Munzone, G. Curigliano, A. H. Partridge. Extended Endocrine Therapy (eET) Following Five Years of Adjuvant LHRH-agonist (LHRHa) in Premenopausal Patients with Node-Positive, Hormone Receptor (HR)-Positive early Breast Cancer (eBC): a subanalysis according to surrogate subtypes 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 PS3-07-09.
Lynce et al. (2026) studied this question.