由于乳腺癌中的 1 型胰岛素样生长因子受体 (IGF-1R) 信号系统在肿瘤增殖和生存中发挥着关键作用，因此长期以来人们一直对它感兴趣。然而，没有 IGF-1R 靶向剂在对照 3 期试验中显示出实质性的临床益处，也没有生物标志物被证明在预测 IGF-1R 靶向剂的益处方面具有临床实用性。 IGFBP7 是一种非典型的胰岛素样生长因子结合蛋白，因为它对 IGF-1R 的亲和力比 IGF 配体更高。我们报告说，低 IGFBP7 基因表达确定了乳腺癌的一个子集，与单独的新辅助化疗相比，在新辅助化疗中添加抗 IGF-1R 单克隆抗体加尼单抗可显着提高病理完全缓解率。在 IGFBP7 表达最低四分位数的患者中，化疗加加尼单抗组的 pCR 率为 46.9%，而最高四分位数的患者的 pCR 率为 5.6%。此外，IGFBP7 高表达预示着远处转移风险增加。如果我们的研究结果得到证实，则应审查停止 IGF-1R 靶向药物开发的决定，该决定是基于先前未使用预测生物标志物的试验的令人失望的结果。© 2024。作者。

There has been a long-standing interest in targeting the type 1 insulin-like growth factor 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 phase 3 trials, and no biomarker has been shown to have clinical utility in the prediction of benefit from an IGF-1R targeting agent. 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 neoadjuvant chemotherapy, substantially improved the pathological complete response rate compared to neoadjuvant chemotherapy alone. The pCR rate in the chemotherapy plus ganitumab arm was 46.9% in patients in the lowest quartile of IGFBP7 expression, in contrast to only 5.6% in the highest quartile. Furthermore, high IGFBP7 expression predicted increased distant metastasis risk. If our findings are confirmed, decisions to halt the development of IGF-1R targeting drugs, which were based on disappointing results of prior trials that did not use predictive biomarkers, should be reviewed.© 2024. The Author(s).