Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer

Insulin-like growth factor 1 (IGF-1) is a potent mitogen for human breast-cancer cells in vitro. In circulation, most of IGF-1 is bound to IGF-binding protein 3 (IGFBP-3). This high-affinity binding is thought to have an important limiting effect on the availability of IGF-1 for biological activity. To assess the availability of IGF-1 for receptor binding, we determined serum levels of IGF-1 and IGFBP-3 and IGF-1/IGFBP-3 ratios. In a case-control study, 150 women aged 38 to 75 years presenting with stage-l or-II breast cancer were investigated just prior to surgery (n = 76), or to irradiation one month after surgery (n = 74). The population-based control group consisted of 441 women of the same age having no breast cancer. Women reporting diabetes mellitus or other hormonal abnormalities were excluded. Premenopausal cases showed elevated IGF-1 serum concentrations, decreased IGFBP-3 levels and increased IGF-1/IGFBP-3 ratios. The IGF-1/IGFBP-3 ratio was a significant breast-cancer risk factor, also after adjustment for age, family history, height, body-mass index, body-fat distribution, and serum levels of C-peptide. The relative risk was 7.34 for the highest compared with the lowest quintile of IGF-1/IGFBP-3. The presence or absence of tumor had no influence on these results. Increased levels of available IGF-1 in the circulation of pre-menopausal women may contribute to the development of breast cancer. © 1995 Wiley-Liss Inc.