ERBB2 and neoplasm: A higher expression of HER2 in tumour cells relative to peripheral tissues is a requirement for the safety and efficacy of trastuzumab and T-DM1, and the loss of HER2 is a known resistance mechanism for trastuzumab.25 A reduction in HER2 expression would be expected to impair T-DM1 binding and internalisation, limiting not only trastuzumab-mediated anti-tumour activity but also the intracellular release and cytotoxicity of DM1.