Understanding the spectrum of HER2 status in breast cancer: From HER2-positive to ultra-low HER2

HER2 (human epidermal growth factor receptor 2) status in breast cancer spans a spectrum from HER2-positive to ultra-low HER2, each category influencing prognosis and treatment decisions differently. Approximately 20 % of breast cancers overexpress HER2, correlating with aggressive disease and poorer outcomes without targeted therapy. HER2 status is determined through immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), guiding therapeutic strategies. HER2-positive breast cancer exhibits HER2 protein overexpression or gene amplification, benefiting from HER2-targeted therapies like trastuzumab and pertuzumab. In contrast, HER2-negative breast cancer lacks HER2 overexpression and amplification, treated based on hormone receptor status. HER2-low breast cancer represents a newly recognized category with low HER2 expression, potentially benefiting from evolving therapies. Ultra-low HER2 cancers, characterized by minimal expression without gene amplification, challenge conventional classifications and treatment paradigms. Their distinct molecular profiles and clinical behaviors suggest unique therapeutic approaches. Recent diagnostic guideline updates refine HER2 assessment, enhancing precision in identifying patients for targeted therapies. Challenges remain in accurately classifying HER2-low tumors and optimizing treatment efficacy, necessitating ongoing research and innovative diagnostic methods. Understanding the heterogeneity and evolving landscape of HER2 status in breast cancer is crucial for advancing personalized treatment strategies and improving patient outcomes.