Clinicopathological Features and Prognostic Impact of Human Epidermal Growth Factor Receptor 2-Low Status in Early-Stage Breast Cancer: A Single-Center Cohort Hormone Receptor-Stratified Retrospective Analysis.

Introduction This study evaluates the prevalence, clinicopathological features, and prognostic impact of human epidermal growth factor receptor 2-low (HER2-low) on breast cancer (BC), focusing on hormone receptor (HR)-stratified outcomes. Materials and methods We retrospectively analyzed 97 patients with HER2-negative invasive BC from 2017 to 2024 at a single center. Data were compared between HER2-low and HER2-0 cohorts, stratified by HR status. Survival outcomes, including disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS), were estimated using Kaplan-Meier methodology. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic effect of HER2-low on DFS. Results The prevalence of HER2-low was 61.9%, with 83.3% of our cases being hormone receptor-positive (HR+). HER2-low/HR+ tumors showed significant disparities in clinical T-stage (p=0.029) compared to HER2-0/HR+ cases. In the hormone receptor-negative (HR-) subgroup, HER2-low tumors exhibited significantly higher lymphovascular invasion (p=0.035) and high cellular proliferation, with all cases having Ki-67 > 20%. In our cohort, lymph node ratio (LNR) risk category and Ki-67 index were identified as the primary independent predictors of DFS. While HER2-low status showed a trend toward increased hazard in univariate analysis, it did not maintain independent significance in the multivariable model (p=0.217). Notably, subgroup analysis demonstrated that the protective effect of HR positivity was significantly more robust within the HER2-low population (p=0.008) compared to the HER2-0 group (p=0.221). Conclusions HER2-low BC is highly prevalent in our cohort but does not independently influence early-stage prognosis. Instead, underlying tumor biology, specifically proliferation (Ki-67) and nodal burden (LNR), remains the primary driver of clinical outcomes. Hormone receptor positivity was associated with favorable survival within the HER2-low subgroup, although non-significant interaction testing underscores that these subgroup observations are exploratory.