Targeting IGF-IR improves neoadjuvant chemotherapy efficacy in breast cancers with low IGFBP7 expression

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• The type 1 insulin-like growth factor receptor (IGF-1R) signaling pathway is crucial for breast cancer proliferation and survival.
• Previous attempts to target IGF-1R in breast cancer have not yielded substantial clinical benefits in phase 3 trials.
• A predictive biomarker for IGF-1R targeting agents has been lacking, hindering clinical development.

Purpose of the Study:

• To investigate the role of insulin-like growth factor binding protein 7 (IGFBP7) as a predictive biomarker for IGF-1R targeting therapy in breast cancer.
• To evaluate the efficacy of ganitumab, an anti-IGF-1R monoclonal antibody, in combination with neoadjuvant chemotherapy based on IGFBP7 expression levels.

Main Methods:

• Analysis of IGFBP7 gene expression in breast cancer patient cohorts.
• Assessment of pathological complete response (pCR) rates in patients receiving neoadjuvant chemotherapy with or without ganitumab.
• Correlation of IGFBP7 expression levels with treatment response and distant metastasis risk.

Main Results:

• Low IGFBP7 gene expression identified a subset of breast cancers with significantly improved pCR rates when treated with ganitumab plus chemotherapy (46.9%) compared to chemotherapy alone (5.6%).
• Conversely, high IGFBP7 expression was associated with a higher risk of distant metastasis.
• IGFBP7 demonstrates potential as a predictive biomarker for response to IGF-1R inhibition.

Conclusions:

• IGFBP7 gene expression can stratify breast cancer patients for response to IGF-1R targeting therapy.
• Low IGFBP7 expression predicts benefit from ganitumab in combination with neoadjuvant chemotherapy.
• Re-evaluation of IGF-1R targeting drug development is warranted, utilizing predictive biomarkers like IGFBP7.