Systemic therapy for metastatic HER2-positive breast cancer

The human epidermal growth factor receptor 2 (HER2), is amplified and/or overexpressed in approximately 15%-20% of breast cancers. Targeting of the HER2 receptor with the humanized monoclonal antibody trastuzumab in combination with chemotherapy has become the backbone of treatment for both early stage and metastatic breast cancer for the last 2 decades. Relapsed or de novo metastatic HER2-positive breast cancer essentially remains an incurable disease. Nonetheless, with advances in therapeutics, survival rates in this group continue to increase with median survival now in excess of 57 months. First line systemic therapy for HER2-positive metastatic breast cancer using taxane chemotherapy combined with trastuzumab and pertuzumab, and second line therapy with trastuzumab emtansine, are well established. Recent studies of small molecule oral tyrosine kinase inhibitors such as tucatinib and neratinib, and antibody drug conjugates such as trastuzumab deruxtecan further improve outcomes. Major treatment challenges remain in the areas of brain metastases and development of drug resistance. This review details an up to date analysis of current and emerging treatments of metastatic HER2-positive breast cancer.