ERBB2 and breast cancer: Details of the combination effect calculation are reported in Additional file 1.Our study of the activation of HER2-dependent signaling in breast cancer cells demonstrated increased levels of Src phosphorylation at tyrosine 416 (Y416) in the lapatinib-resistant cells (MDA-MB-361-LR and JIMT-1), whereas levels of phosphorylated HER2 were unchanged (Figure 1B).