EFFECT OF FENRETINIDE ON PLASMA IGF-I AND IGFBP-3 IN EARLY BREAST-CANCER PATIENTS

Growing evidence substantiates the role of the insulin-like growth fac tor 1 (IGF-I) system in breast tumorigenesis. Retinoids have been show n to affect the IGF system in several experimental models. We extended our previous data on plasma IGF-I modulation by the synthetic retinoi d fenretinide (4-HPR) and investigated the effect of the retinoid on p lasma IGF binding protein (BP)-3, the major protein binding IGFs. IGF- I and IGFBP-3 were measured on plasma samples obtained at randomizatio n and after an interval of approximately 1 year, from 39 and 33 stage 1 breast cancer patients assigned to receive 4-HPR, and from 39 and 34 untreated controls, respectively, There was a significant decrease in plasma IGF-I after 4-HPR administration, whereas no significant chang e was observed in controls. The effect of 4-HPR on IGF-I levels was mo dified by menopausal status, inasmuch as the decrease in IGF-I was par ticularly pronounced in premenopausal women, whereas the reverse was o bserved in untreated controls. By contrast, treatment induced an incre ase of IGFBP-3 with respect to controls. As a result of this dual effe ct, the bioavailability of IGF-I for interaction with receptors at tar get levels further decreased in pre-menopausal 4-HPR-treated patients compared with controls, suggesting that retinoid administration may re sult in lower concentrations of biologically active IGF-I. Our finding s may have important implications for the clinical preventive activity of this retinoid. (C) 1998 Wiley-Liss, Inc.