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 factor I (IGF-1) system in breast tumorigenesis. Retinoids have been shown to affect the IGF system several experimental models. We extended our previous data on plasma IGF-1 modulation by the synthetic retinoid fenretinide (4-HPR) and investigated the effect of the retinoid on plasma IGF binding protein (BP)-3, the major protein binding IGFs. IGF-1 and IGFBP-3 were measured on plasma samples obtained at randomization 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-1 after 4-HPR administration, whereas no significant change was observed in controls. The effect of 4-HPR on IGF-1 levels was modified by menopausal status, inasmuch as the decrease in IGF-1 was particularly pronounced in pre-menopausal women, whereas the reverse was observed in untreated controls. By contrast, treatment induced an increase of IGFBP-3 with respect to controls. As a result of this dual effect, the bioavailability of IGF-1 for interaction with receptors at target levels further decreased in pre-menopausal 4-HPR treated patients compared with controls, suggesting that retinoid administration may result in lower concentrations of biologically active IGF-1. Our findings may have important implications for the clinical preventive activity of this retinoid.
Torrisi
R
R
Department of Medical Oncology II, National Institute for Cancer Research, Genoa, Italy.
Parodi
S
S
Fontana
V
V
Pensa
F
F
Casella
C
C
Barreca
A
A
De Palo
G
G
Costa
A
A
Decensi
A
A
D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000097:blood*; D005260:Female; D017313:Fenretinide / Q000494:pharmacology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008875:Middle Aged
D016588:Anticarcinogenic Agents; D018972:Insulin-Like Growth Factor Binding Protein 3; D017313:Fenretinide; D007334:Insulin-Like Growth Factor I