In breast cancer cells BT474 (ER and HER2 positive) and SKBR3 (ER negative, HER2 positive) exposed long-term to EGFR-targeted small molecules (gefitinib, erlotinib) and colon cancer cells SW48 exposed long-term to anti-EGFR monoclonal antibody cetuximab, the development of resistance was analyzed. The gene discussed is EGFR; the disease is breast cancer.