Several potential mechanisms of the trastuzumab resistance have been proposed: (1) HER2 heterogeneity, (2) loss of HER2 positivity/acquired HER2 mutations, (3) HER2 heterodimers, (4) altered intracellular signaling, and (5) the tumor immune microenvironment.6 Among these mechanisms, the tumor immune microenvironment is crucial for regulating the antitumor efficacy of trastuzumab. The gene discussed is ERBB2; the disease is neoplasm.