To explore mechanisms of resistance to T‐DM1, the MDA‐MB‐361 HER2‐positive breast cancer cell line was exposed in vitro to T‐DM1 in the absence or presence of ciclosporin A. Previously reported mechanisms of resistance such as trastuzumab‐binding alterations, MDR1 upregulation, and SLC46A3 downregulation were not observed in these models. Here, SLC46A3 is linked to breast carcinoma.