Exploring Human Epidermal Growth Factor Receptor 2 (HER2)-Low Early Breast Cancer in a Moroccan Population: Clinical Characteristics and Survival Outcomes

Abstract

Breast cancers with low human epidermal growth factor receptor 2 (HER2) expression, classified as an immunohistochemistry (IHC) score of 1+ or 2+ without gene amplification, have recently drawn increased interest due to the emergence of novel anti-HER2 therapies. However, there is still debate over whether HER2-low tumors form a distinct category. This study set out to examine and compare the clinical characteristics and outcomes of early-stage breast cancer patients with HER2-zero and HER2-low expression. We reviewed medical records of stage I-III patients treated at Souss-Massa University Hospital Center in Morocco between 2016 and 2018. HER2-positive cases were excluded, leaving two comparison groups: HER2-zero and HER2-low. Using statistical methods, we assessed baseline characteristics and survival outcomes - disease-free survival (DFS) and overall survival (OS) - through Kaplan-Meier analysis, log-rank testing, and Cox regression models based on key prognostic factors like age, hormone receptor (HR) status, Ki-67 index, and lymph node involvement. Among 322 patients studied, we found 114 were HR-positive/HER2-zero, 95 HR-positive/HER2-low, 85 HR-negative/HER2-zero, and 28 HR-negative/HER2-low. Tumor size, nodal status, and histologic grade were similar across both groups. Notably, HER2-low tumors were more often HR-positive (95 (77.2) vs. 114 (57.3), p < 0.001), and HER2-zero tumors were more likely to have high Ki-67 levels (>20%) (95 (47.73) vs. 41 (33.33), p = 0.009). While certain subgroups, like HR-positive or high Ki-67 cases, showed better DFS in the HER2-low group, overall, there were no significant differences in DFS or OS. These results suggest HER2-low and HER2-zero breast cancers share largely similar features and outcomes; however, in certain subgroups, HER2-low tumors were associated with significantly better DFS, possibly reflecting differences in tumor biology. Further research is essential to clarify the biological role of HER2-low expression.