IGFBP3 and breast carcinoma: Consistent with this, loss of IGFBP-3 expression and consequent derepression of IGF1R signaling have been suggested to account for acquired resistance to the EGFR tyrosine kinase inhibitor gefitinib [9]. In vitro studies in breast cancer cells have also indicated that the efficacy of some anticancer agents, including retinoic acid, antiestrogens, and tumor necrosis factor-alpha (TNFα), is in part mediated by IGFBP-3 [10–13].