These mechanisms include HER2 mutations, abnormal activation of HER2 downstream or bypass signaling pathways, and immune suppression within the tumor microenvironment (TME).[5] Yet, primary trastuzumab resistance is attributed to inherent properties of cancer cells, which mainly caused by mutation and gene rearrangement of HER2 and members of relevant signal cascades,[7, 8] while secondary trastuzumab resistance results from adaptive changes that occur during long‐term treatment, which can be likened to an evolutionary process with selective pressure. This evidence concerns the gene ERBB2 and cancer.