New HER2-positive targeting agents in clinical practice.

Overexpression of human epidermal growth factor occurs in approximately 20-25 % of invasive breast cancers. This subtype of breast cancer has been associated with poor clinical outcomes. The development of trastuzumab, a humanized monoclonal antibody that binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2), revolutionized outcomes of patients with HER2-positive breast cancer; however, many patients with HER2-positive metastatic breast cancer eventually become resistant to it. Several newer anti-HER2 agents have been developed, including lapatinib, pertuzumab, and trastuzumab emtansine. These exciting advances in drug development for HER2-positive breast cancer have also led to many challenges, including how to optimally sequence and combine HER2-targeted agents.