Focusing on the Advances and Challenges of HER2-Targeted Therapy: Cutting-Edge Breakthroughs in Neoadjuvant Treatment for HER2-Positive Breast Cancer.

HER2-positive breast cancer, characterized by overexpression of the human epidermal growth factor receptor 2 (HER2), accounts for approximately 15-20% of all breast cancers and is associated with aggressive tumor behavior and poor prognosis. Advances in HER2-targeted therapies, such as monoclonal antibodies (trastuzumab, pertuzumab), tyrosine kinase inhibitors (TKIs), and antibody-drug conjugates (ADCs), have significantly improved treatment outcomes in this subtype. Neoadjuvant therapy, administered before surgery, has become a cornerstone in managing HER2-positive breast cancer by improving pathological complete response (pCR) rates and survival outcomes. This review provides a comprehensive analysis of recent advancements in HER2-targeted neoadjuvant therapies, highlighting the mechanisms of action, clinical efficacy, and synergistic effects when combined with chemotherapy. Key challenges, such as treatment-related toxicities, and the potential for personalized treatment strategies based on biomarkers like tumor-infiltrating lymphocytes (TILs) and HER2-enriched subtypes, are discussed. Future directions emphasize optimizing treatment regimens to enhance efficacy while minimizing adverse effects, with novel agents such as trastuzumab deruxtecan (T-DXd) showing promise for expanding the therapeutic landscape.