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.