Lisa Carey, MD, FASCO, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, discusses the recently published findings of the Phase III CALGB 40601 Alliance study (NCT00770809), evaluating survival, pathologic response, and genomics in patients with HER2-positive breast cancer treated with paclitaxel-trastuzumab with or without lapatinib. Dual HER2-targeting resulted in significant relapse-free survival (RFS) and overall survival benefits, and the integration of intrinsic subtype and immune signatures resulted in prediction of pathological complete response (pCR) and RFS, providing rationale for escalation or de-escalation approaches in HER2-positive disease. This interview took place during the 17th St. Gallen International Breast Cancer Conference.