In a HER2 overexpressing and trastuzumab resistant preclinical breast cancer model, targeted treatment with ado-trastuzumab emtansine (T-DM1) in combination with anti-PD1 antibody or anti-CTLA-4 antibody showed enhanced anti-tumor efficacy, T cells trafficking in to the tumor and Th1 cell polarization (58). This evidence concerns the gene CTLA4 and breast cancer.