Updates on the treatment of human epidermal growth factor receptor type 2-positive breast cancer

PURPOSE OF REVIEW: To review the most recent developments in the treatment of human epidermal growth factor receptor type 2 (HER2)-positive breast cancer with novel HER2-targeting agents and combinations that have significantly improved clinical outcomes. RECENT FINDINGS: Since the approval of trastuzumab 15 years ago, the natural history of HER2-positive breast cancer has been altered with improvements in survival for both early and advanced disease with the addition of this agent to standard chemotherapy. The HER2 receptor pathway drives breast cancer growth and aggressiveness, and HER2-targeted agents can improve survival in early and advanced disease. In the advanced setting, two new drugs have been approved since 2012, pertuzumab and ado-trastuzumab emtansine (T-DM1), both of which improve survival without any reciprocal increase in toxicity. However, resistance almost always ensues, pointing to the need to understand the driving mechanisms and to biomarkers that will help individualize therapy and point to newer signal transduction and other modulators. SUMMARY: HER2-positive breast cancer represents a distinct subtype with more aggressive clinical characteristics. HER2-targeted therapies, usually in combination with chemotherapy, are the standard of care, improving the cure rate in early-stage breast cancer and lengthening survival in the advanced setting.