Clinicopathological characterization of HER2-low breast cancer

Abstract

Breast cancer continues to be one of the most prevalent and deadly malignancies affecting women across the globe, with ongoing research emphasizing the need for refined subclassification to enhance clinical outcomes. The introduction of the HER2-low breast cancer category-defined by immunohistochemistry scores of 1+ or 2+ with a negative result on in situ hybridization-has prompted new investigations into its biological and clinical relevance. HER2-low tumors are believed to fill the spectrum between traditional HER2-negative and HER2-positive subtypes, yet their true characteristics, prognostic significance, and therapeutic implications remain partially understood. In this retrospective study, 207 cases of invasive breast carcinoma were evaluated from a single institution, with tumors classified into HER2-negative, HER2-low, and HER2-positive groups. Comprehensive clinicopathological and molecular data were collected and compared, including demographic variables, tumor size, histological grade, lymph node status, hormone and proliferation marker expression, and prognostic scores. The results demonstrate that HER2-low breast cancers represent a substantial fraction of cases, most commonly occurring in hormone receptor-positive patients. No statistically significant differences emerged between HER2-low and HER2-negative cancers regarding most clinical or pathological parameters; however, HER2-positive tumors correlated with higher grade and less favorable prognosis. Subgroup and stratified analyses reinforced the considerable overlap between HER2-low and HER2-negative cancers, challenging the notion of complete biological distinction. Nevertheless, the identification of HER2-low status is clinically meaningful given the proven benefits of recently developed targeted therapies such as trastuzumab deruxtecan, which have expanded treatment options for a broader patient population. These findings highlight the importance of standardized, accurate HER2 assessment and ongoing efforts in molecular profiling to further clarify the role of HER2-low tumors in breast cancer heterogeneity and personalized care.