In this study, we characterize the molecular changes in HER2 overexpressing breast cancer cell lines that are sensitive (BT474 breast ductal carcinoma lineage cell lines) and resistant (BT474R) to anti-HER2 treatment when stimulated with two major ligands involved in HER2 signaling—EGF and HRG. The gene discussed is ERBB2; the disease is breast carcinoma.