Low IGFBP7 expression identifies a subset of breast cancers with favorable prognosis and sensitivity to IGF-1 receptor targeting with ganitumab: Data from I-SPY2 and SCAN-B

There has been a long-standing interest in targeting the insulin-like growth factor-1 receptor (IGF-1R) signaling system in breast cancer due to its key role in neoplastic proliferation and survival. However, no IGF-1R targeting agent has shown substantial clinical benefit in controlled trials, and no treatment predictive biomarkers for IGF-1R targeting agents exist. IGFBP7 is an atypical insulin-like growth factor binding protein as it has a higher affinity for the IGF-1R than IGF ligands. We report that low IGFBP7 gene expression identifies a subset of breast cancers for which the addition of ganitumab (an anti-IGF-1R monoclonal antibody) to chemotherapy substantially improved the pathological complete response rate compared to neoadjuvant chemotherapy alone. Furthermore, high IGFBP7 expression predicted increased distant metastasis risk. If our findings are confirmed, decisions to halt the development of IGF-1 targeting drugs, which were based on disappointing results of prior trials that did not use predictive biomarkers, should be reviewed.