ERBB2 and breast carcinoma: Poor HER2-DM1 complex internalization, defective intracellular and endosomal trafficking of the HER2-DM1 complex, defective lysosomal degradation of T-DM1, and drug efflux proteins, such as MDR1, are among the mechanisms of T-DM1 resistance.[20,21] Following the approval of T-DM1, ADC development has become a crucial therapeutic strategy for HER2-positive breast cancer.