ERBB2 and breast cancer: We predict lack of responsiveness to HER2-targeted therapies among these patients whose cancers lack HER2-amplification, consistent with previous trials of lapatinib9 and, more recently, the NSABP-B47 trial of adjuvant trastuzumab in 3270 patients with breast cancers having weakly positive HER2 expression by IHC (1+) or moderately positive HER2 expression by IHC (2+) but HER2-not-amplified (HER2-negative) by FISH.43 Therefore, use of HER2-directed therapies in a population falsely classified as HER2-positive is expected to produce inferior clinical and pharmacoeconomic outcomes.