The Role of Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Therapies in Early-Stage Breast Cancer: Current Practices, Treatment De-escalation, and Future Prospects

Human epidermal growth factor receptor 2 (HER2)-targeted therapy has transformed the treatment paradigm for early-stage HER2-positive breast cancer, providing personalized and effective interventions. This comprehensive review delves into the current state of HER2-targeted therapies, emphasizing pivotal clinical trials that have demonstrated their substantial impact on long-term outcomes. Combination therapies that integrate HER2-targeted agents with chemotherapy exhibit enhanced tumor responses, particularly in neoadjuvant settings. Neoadjuvant chemotherapy (NACT) is explored for its role in tumor downsizing, facilitating breast-conserving surgery (BCS), and incorporating oncoplastic solutions to address both oncologic efficacy and aesthetic outcomes. Innovative axillary management post-NACT, such as targeted axillary dissection (TAD), is discussed for minimizing morbidity. The review further explores the delicate balance between maximal therapy and de-escalation, reflecting recent trends in treatment approaches. The therapeutic landscape of HER2-low breast cancer is examined, highlighting considerations in HER2-positive breast cancer with BReast CAncer gene (BRCA) mutations. Emerging immunotherapeutic strategies, encompassing immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy, are discussed in the context of their potential integration into treatment paradigms. In conclusion, the evolving landscape of HER2-positive early-stage breast cancer treatment, characterized by targeted therapies and multidisciplinary approaches, underscores the need for ongoing research and collaborative efforts. The aim is to refine treatment strategies and enhance patient outcomes in this dynamic and rapidly evolving field.