ERBB2 and breast cancer: Indeed, there is a growing necessity to discover the resistance mechanisms of the FDA-approved anti-HER2 TKIs and therapeutic strategies to overcome it, since they have advantageous characteristics (such as oral administration, capability to reach CNS metastasis, multiple HER family targets, lower cardiotoxicity), and importantly they are the therapeutic alternatives to the treatment of anti-HER2 antibodies-refractory HER2 + breast cancer patients [17].