Previous work from our laboratory had shown that heregulin β1 (HRG), a soluble ligand for HER3 and HER4, but not an EGFR ligand (EGF), can abrogate the inhibitory effects of lapatinib on cell-signaling pathways in parental HER2+ breast cancer cells [44,45], findings that were recently confirmed by Settleman and colleagues [46]. Here, HRG is linked to breast cancer.