HER2 Heterogeneity in Breast Cancer: Biological Basis, Clinical Implications, and Therapeutic Strategies

Human epidermal growth factor receptor 2 (HER2) is a key driver of breast cancer and exhibits significant heterogeneity at the temporal, spatial, and molecular levels. This heterogeneity not only complicates HER2 assessment but also significantly impacts the efficacy of targeted therapies, ultimately contributing to drug resistance. This review summarizes current standards for HER2 testing and highlights their inherent limitations. It outlines the multidimensional manifestations of HER2 heterogeneity and examines the underlying biological mechanisms driving this phenomenon. In addition, emerging diagnostic strategies and therapeutic approaches are being developed specifically to address HER2 heterogeneity. The review aims to provide insights for optimizing patient stratification and advancing precision treatment in breast cancer.