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.

Authors

Mai A Abdelazez, Ahmed M Hammad, Bashayer Alenazi, Laila Moharram, Omar Alzahrani

Published in

Cureus. Volume 18. Issue 8. Pages e114911. Epub Aug 21, 2026.

Abstract

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.

PMID:
42764880
Bibliographic data and abstract were imported from PubMed on 21 Sep 2026.

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