Pre-clinical studies have also revealed multiple mechanisms, including a decrease in HER2 overexpression in HER2-positive breast cancer cells, contribute to resistance to T-DM19–12, while no major changes in HER2 expression in T-DM1-resistant clones, which are derived from HER2-positive breast cancer cells (BT-474), are observed compared with BT-474 parental cells12. Here, ERBB2 is linked to breast carcinoma.