Abstract PS3-07-29: Real-world outcomes by Estrogen Receptor Expression Subgroups in Patients with HER2-negative Breast Cancer: A Population-based Cohort Study

Abstract Background: In Sweden, patients with breast cancer (BC) expressing 10-100% estrogen receptor (ER) are treated as ER-positive, whereas those with ER-low (1-9%) BC are managed as triple-negative disease (TNBC). The distinct clinicopathological and prognostic significance of ER-subgroups, especially low and intermediate ER-expressing BC, remains incompletely characterized. We aimed to describe real-world patient and tumor characteristics, treatment patterns and overall survival across ER subgroups in a Swedish population-based cohort of patients with HER2-negative BC. Methods: In this nationwide cohort study, all Human Epidermal growth factor Receptor 2 (HER2)-negative BC patients diagnosed in Sweden (2007-2023) were stratified by ER status: ER-zero (0%), ER-low (1-9%), ER-sublow (10-29%), ER-medium (30-59%; ER-med), and ER-high positive (60-100%; ER-high). Cohorts were analyzed separately for adjuvant and neoadjuvant settings. Overall survival (OS) was evaluated using Kaplan-Meier analysis and multivariable Cox proportional hazards models. Models were adjusted for age, year of diagnosis, tumor stage, grade, and treatment modality. Results: We analyzed 75,473 eligible patients, stratified into adjuvant (n = 70,159: ER-zero = 4,559; ER-low = 536; ER-sublow = 504; ER-med = 1,425; ER-high = 63,135) and neo-adjuvant cohorts (n = 5,314; ER-zero = 1,766; ER-low = 205; ER-sublow = 132; ER-med = 145; ER-high = 3,066). ER-sublow demonstrated significantly worse OS than higher ER expression subgroups in the adjuvant cohort. In univariable analysis, ER-sublow patients had 1.27-fold increased mortality risk versus ER-med (hazard ratio (HR) = 1.27, 95% confidence interval (CI) = 1.04-1.55, p = 0.017) and 1.63-fold increased risk versus ER-high (HR = 1.63, 95% CI = 1.37-1.93, p 0.001). ER-sublow showed no significant difference in OS compared to ER-zero (HR = 0.86, 95% CI = 0.72-1.03, p = 0.106) or ER-low (HR = 1.12, 95% CI = 0.88-1.43, p = 0.347). Multivariable analysis confirmed significantly poorer survival for ER-sublow versus ER-high (adjusted HR = 1.58, 95% CI = 1.33-1.88, p 0.001). Notably, ER-med demonstrated worse OS compared to ER-high in both univariable analysis (HR = 1.19, 95% CI = 1.08-1.32, p 0.001) and multivariable analysis (adjusted HR = 1.26, 95% CI = 1.13-1.39, p 0.001). No significant survival differences were observed between ER subgroups in the neo-adjuvant cohort (all p 0.05). Conclusion: ER-sublow (10-29%) patients have characteristics and prognosis similar to patients with ER-low (1-9%) and ER-zero BC, while patients with ER-med (30-59%) BC have inferior outcomes than patients with ER-high (60-100%) BC. ER expression should be considered as a continuum rather than a binary (positive/negative) biomarker in clinical decision-making. Citation Format: q. yang, X. Chen, J. Hartman, B. Acs. Real-world outcomes by Estrogen Receptor Expression Subgroups in Patients with HER2-negative Breast Cancer: A Population-based Cohort 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 PS3-07-29.