The insulin-like growth factor system in advanced breast cancer.

Despite improvements in therapy, the prognosis for advanced breast cancer is poor and a search for new treatment targets and key regulators of tumour growth is warranted. Extensive data are available on the importance of the insulin-like growth factor (IGF) system in growth regulation of breast cancer cell lines in vitro, indicating that the IGF-I receptor (IGF-IR), IGF-I (and IGF-II) function as survival factors, while IGF binding protein (IGFBP)-3 may act as a growth inhibitor. There is a tight link between the growth regulatory pathways of IGFs and oestrogens in oestrogen-receptor(OR)-positive breast cancer cells. In vivo studies indicate a role of IGF-I and IGF-IR in breast cancer development. However, the importance of the IGF system in metastatic and highly aggressive breast tumours in vivo is not clear, and therapeutic strategies designed to interrupt IGF signalling have not yet proved to be an effective treatment modality in patients with metastatic breast cancer.