ABSTRACT
Trastuzumab combined with chemotherapy improves overall response rate in women with HER2-overexpressing breast cancer.However,therapeutic resistance to trastuzumab typically occurs after several months of starting therapy and overall survival does not improve significantly.Studies have reported that the potential mechanisms of resistance to trastuzumab are mainly related to the signal pathway activation from receptor tyrosine protein kinases outside of the HER family and the amplification of the PI3K-AKT pathway.Novel target therapies such as tyrosine kinase inhibitors,PI3K inhibitors are approved as substitutes for the treatment of HER2-overexpressing breast cancer,but the response to each single-agent tends to be short-lived.Several large randomized adjuvant trials have showed that novel molecular targeted therapies combinations will markedly limit or eventually abrogate acquired resistance to primary trastuzumab therapy.