Her2 cross talk and therapeutic resistance in breast cancer.

The HER2 receptor tyrosine kinase is amplified and/or overexpressed in approximately 30 percent of metastatic breast cancers. Interactions and cross signaling from the HER2 receptor to other growth factor receptors may potentially contribute to therapeutic resistance. In this review, we discuss HER2 receptor cross talk with the estrogen receptor and implications toward resistance to endocrine therapies. We also review mechanisms of resistance to the HER2-targeted antibody trastuzumab, including signaling from other members of the HER family, increased signaling through the PI3-kinase pathway, and cross talk from the insulin-like growth factor-I receptor to HER2. Finally, we will provide perspective on how HER2 receptor cross talk may provide critical information for developing novel therapeutic options for HER2-overexpressing breast cancers.