Collectively, our studies suggest that the combinations of MM-121 and trastuzumab inhibited proliferation of both trastuzumab-sensitive and trastuzumab-resistant breast cancer cells mainly through cell cycle G1 arrest, which was correlated with the upregulation of p27kip1 and sometimes a concomitant downregulation of E2F-1. This evidence concerns the gene E2F1 and breast carcinoma.