Management of patients with HER2-positive metastatic breast cancer: is there an optimal sequence of HER2-directed approaches?

The successful development of therapies targeting the human epidermal growth factor receptor 2 (HER2) has altered the natural progression of disease among patients with HER2-positive metastatic breast cancer. The monoclonal antibody trastuzumab was the first HER2-directed agent and it was associated with significantly improved outcomes for patients. Subsequently, other HER2-directed agents such as the monoclonal antibody pertuzumab, the tyrosine kinase receptor inhibitor lapatinib, and the immunoconjugate trastuzumab emtansine were developed to overcome resistance to trastuzumab and provide additional treatment options for patients. Recent data have demonstrated that the use of these HER2-directed agents improves outcomes. However, with the emergence of new HER2-targeted agents, the optimal sequencing of treatment remains unclear. Ongoing research is investigating new HER2 combinations, the role of sequencing, novel HER2-directed agents, and combinations with other targeted agents to overcome resistance. Cancer 2015;121:17-24. (c) 2014 American Cancer Society. The successful development of therapies targeting the human epidermal growth factor receptor 2 (HER2) has altered the natural progression of disease among patients with HER2-positive metastatic breast cancer. This review focuses on the HER2-directed agents currently available in clinical practice and the literature regarding the optimal sequencing of these agents.