We have published a series of articles [31,32,75,76] indicating that estrogenic promotion of erbB2 kinase activity in mammary tumor cells requires erbB3, and the activation of erbB3 signaling plays an essential role in erbB2-mediated therapeutic resistance to tamoxifen, trastuzumab, and paclitaxel (Figure 1). The gene discussed is ERBB2; the disease is breast cancer.