ERBB2 and breast cancer: The anti-tumor activity and favorable tolerability of dual HER2 blockade with TKI plus trastuzumab has been reported previously and mechanisms of synergistic interaction may involve enhanced apoptosis of cancer cells, increased stabilization and degradation of HER2 receptors, and reversion of resistance to trastuzumab by accumulation of HER2 receptors on the surface of breast cancer cells [20, 21].