Pathologic complete response (pCR) was noted to be prognostic in all but hormone receptor-positive (HR) breast cancer cases even when HER2 is overexpressed. Evocative data suggest that HER2-positive breast cancer patients are a heterogeneous population and a subset of HER2-positive and HR-positive tumors biologically behave more like HER2-negative. Identification and targeted monitoring of these patients is crucial to consolidate data aiming to optimize combination treatment with new agents, thereby avoiding overtreatment with chemotherapy. The questions surrounding HER2-positive and HR-positive breast cancer patients treatment as well as the potential direction towards development of surrogate markers alternative to pCR are discussed
