IGF-1 receptor activation and intrinsic tamoxifen resistance in postmenopausal breast cancer patients.

544 Background: Elevated insuline-like growth factor 1 receptor (IGF-1R) signaling activates the phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways and results in hormone indepedent cell growth in vitro, rendering cells resistant to anti-estrogens. The clinical validity of IGF-1R signaling to predict resistance to adjuvant anti-estrogen therapy has not been well established.We tested the predictive value of IGF-1R activation to predict adjuvant tamoxifen resistance in postmenopausal breast cancer patients. Methods: We collected primary tumor blocks from 563 ERα positive (stage I-III) postmenopausal patients who had been randomized between tamoxifen (1 to 3 years) vs. no adjuvant therapy (IKA trial). The median follow-up of patients without a recurrence event was 7.8 years. Immunohistochemistry was performed on a tissue microarray using monoclonal antibodies for IGF-1R and phosphorylated(p)-IGF-1R. Cytoplasmic p-IGF-1R and membranous IGF-1R intensity were scored (0-3)...