Proliferation-Guided Risk Stratification in HER2-Low vs. HER2-Positive Hormone Receptor-Positive Breast Cancer: A Multicenter Retrospective Analysis

OpenAlex İngilizce

INTRODUCTION: HER2-low breast cancer is a newly characterized subgroup with unclear prognostic implications. This study investigates the prognostic role of Ki67 in hormone receptor-positive (HR+) HER2-low and HER2-positive breast cancer. METHODS: We retrospectively analyzed 224 HR+ breast cancer patients from four tertiary centers (96 HER2-low, 128 HER2-positive). Patients were stratified into stages 1-3 (n = 156) and stage 4 (n = 68). Survival outcomes were assessed according to HER2 and Ki67 status using Kaplan-Meier analysis and Cox regression. RESULTS: HER2-low patients were older (≥65 years: 65% vs. 28%, p < 0.001). In stage 1-3 patients, disease-free survival (DFS) was significantly longer in the HER2-low subgroup (median: 86 vs. 59 months; p < 0.001) and in those with Ki67 < 20% (median: 74 vs. 34 months; p < 0.001). Multivariable analysis confirmed high Ki67 (HR: 1.664; 95% CI: 1.564-2.048; p < 0.001), hormone receptor negativity (HR: 1.967; 95% CI: 1.614-2.433; p = 0.020), larger tumor size, and axillary nodal involvement as independent predictors of poor DFS. Among stage 4 patients, overall survival (OS) did not differ significantly by HER2 status (34 vs. 28 months; p = 0.427) but was significantly shorter in those with Ki67 ≥ 20% (18 vs. 29 months; p < 0.001). In multivariable analysis, high Ki67 (HR: 2.174; 95% CI: 1.994-2.256; p < 0.001), hormone receptor negativity (HR: 1.649; 95% CI: 1.184-2.143; p < 0.001), and presence of brain metastasis (HR: 1.564; 95% CI: 1.379-1.994; p < 0.001) were independent predictors of poor OS. CONCLUSION: Ki67 appears to be an important prognostic biomarker in HR+ breast cancer across both HER2-low and HER2-positive subgroups. Dual stratification by HER2 and Ki67 status may improve risk assessment and help identify high-risk subgroups who could benefit from treatment approaches beyond endocrine therapy alone. These findings warrant confirmation in prospective studies.