Advances in the Treatment of Early-Stage HER2-Positive Breast Cancer

The management of early-stage human epidermal growth factor receptor 2-positive (HER2+) breast cancer has evolved in recent years, with the current standard being to tailor the intensity of adjuvant treatment to individual risk. Risk-adapted approaches to systemic therapy have been facilitated both by the recent introduction of multiple novel HER2-targeted therapies and by the development of clinical and pathologic surrogates to enable better prediction of disease behavior. These approaches have been successful at both ends of the disease spectrum. Patients with low-risk tumors now experience excellent long-term outcomes and reduced toxicity after de-escalated adjuvant therapy, and patients with high-risk residual disease after neoadjuvant systemic therapy have had a significant decrease in the risk for disease recurrence with the escalation of adjuvant therapy, including the use of trastuzumab emtansine (also known as T-DM1). We review here key developments in neoadjuvant and adjuvant systemic therapy for early-stage HER2+ breast cancer and provide an overview of the current standards of management, incorporating recent advances in escalation and de-escalation approaches for higher- and lower-risk disease, respectively. We also discuss areas of ongoing clinical uncertainty, including how disease heterogeneity and hormone receptor status affect the selection of treatments and the selection of patients for chemotherapy-free approaches. Finally, we review ongoing areas of active investigation and unmet clinical needs in this patient population.