INSULIN-LIKE GROWTH-FACTOR-BINDING PROTEIN-3 IS DECREASED IN EARLY-STAGE OPERABLE PREMENOPAUSAL BREAST-CANCER

Insulin-like growth factor I (IGF-I) is a potent mitogen for human bre ast-cancer cells in vitro. In circulation, most of IGF-I is bound to I GF-binding protein 3 (IGFBP-3). This high-affinity binding is thought to have an important limiting effect on the availability of IGF-I for biological activity. To assess the availability of IGF-I for receptor binding, we determined serum levels of IGF-I and IGFBP-3 and IGF-I/IGF BP-3 ratios. In a case-control study, 150 women aged 38 to 75 years pr esenting with stage-I or -II breast cancer were investigated just prio r to surgery (n = 76), or to irradiation one month after surgery (n = 74). The population-based control group consisted of 44 women of the s ame age having no breast cancer. Women reporting diabetes mellitus or other hormonal abnormalities were excluded. Premenopausal cases showed elevated IGF-I serum concentrations, decreased IGFBP-3 levels and inc reased IGF-I/IGFBP-3 ratios. The IGF-I/IGFBP-3 ratio was a significant breast-cancer risk factor, also after adjustment for age, family hist ory, 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-I/IGFBP-3. The presence or absence of tumo r had no influence on these results. Increased levels of available IGF -I in the circulation of pre-menopausal women may contribute to the de velopment of breast cancer. (C) 1995 Wiley-Liss, Inc.