ERBB2 and breast cancer: HER4 signaling may also be a mechanism of resistance: Canfield et al. showed that HER2+ breast cancer cell line models of lapatinib and trastuzumab resistance (BT474-LR, SKBR3-TR, SKBR3-LR, and SKBR3-LTR) were dependent on HER4 expression for survival, unlike their parent cell lines [108].