HER2-Low Breast Cancer: Where Are We?

BackgroundBreast cancer is traditionally classified into three clinical subtypes based on hormone receptor and HER2 status (i.e., luminal-like, HER2-positive and triple negative). Each subtype has distinct clinical-pathological and molecular characteristics and requires tailored treatments. Recent research efforts have been focusing on a new classification, identifying the so-called "HER2-low" category, including tumors characterized by a low level of HER2 expression (immunohistochemistry score 1 + or 2+ without ISH amplification). Emerging evidence shows that also patients with HER2-low tumors can derive benefits from selected anti-HER2 therapies. This represents a major advance in the field of breast oncology, where a broader proportion of patients with breast cancer can ultimately benefit from new effective targeted treatment strategies. SummaryThe antibody drug conjugate trastuzumab deruxtecan has proven impressive efficacy in patients with HER2-low breast cancer, and several other drugs are currently under investigation in this subset of patients. Additional investigation is needed to address open issues that still exist in this topic, including appropriate pathological assessment of HER2-low status, clarification of its prognostic implications, and global access to newly approved drugs. Key message Our review aims to summarize the available evidence regarding HER2-low breast cancer, illustrating the current challenges that are being addressed and the future perspectives in this exciting new field.