Cancer Epidemiology Biomarkers & Prevention Vol. 10, 1047-1053, October 2001 © 2001 American Association for Cancer Research Long-Term Effects of Fenretinide, a Retinoic Acid Derivative, on the Insulin-like Growth Factor System in Women with Early Breast Cancer 1Andrea Decensi2, Harriet Johansson, Rosalba Miceli, Luigi Mariani, Tiziana Camerini, Elena Cavadini, Maria Gaetana Di Mauro, Antonina Barreca, Aliana Guerrieri Gonzaga, Silvia Diani, Maria Teresa Sandri, Giuseppe De Palo and Franca Formelli Division of Chemoprevention [A. D., A. G. G., S. D.], Laboratory Medicine Unit [H. J., M. T. S.], European Institute of Oncology, 20141 Milan; Unit of Medical Statistics and Biometry [R. M., L. M.], Unit of Controlled Clinical Trials [T. C.], Chemoprevention Unit [F. F., E. C.], Division of Clinical Oncology [M. G. D. M., G. D. P.], Istituto Nazionale Tumori, 20133 Milan; and Department of Endocrinology and Metabolic Sciences, University of Genoa, 16132 Genoa [A. B.], Italy High insulin-like growth factor-I (IGF-I) levels are associated with an increased risk of breast cancer in premenopausal women. Because the synthetic retinoid fenretinide showed a beneficial effect on second breast cancers in premenopausal women in a Phase III trial, we studied its long-term effects on IGF-I levels. We measured, at yearly intervals for up to 5 years, the circulating levels of IGF-I, IGF binding protein (BP)-3, and their molar ratio in 60 subjects 50 years of age and 60 subjects >50 years of age allocated either to fenretinide or no treatment. In women 50 years of age, measurements of IGF-II, IGFBP-1, and IGFBP-2 were also performed. The associations between biomarkers and drug or metabolite plasma concentrations were also investigated. All biomarkers were relatively stable over 5 years in the control group. Compared with controls and after adjustment for baseline, treatment with fenretinide for 1 year induced the following changes: IGF-I, -13% [95% confidence interval (CI), -25 to 1%] in women 50 years of age and -3% (95% CI, -16 to 13%) in women >50 years of age; IGFBP-3, -4% (95% CI, -12 to 6%) in both age groups; IGF-I:IGFBP-3 molar ratio, -11% (95% CI, -22 to 1%) in women 50 years of age and 1% (95% CI, -11 to 16%) in women >50 years of age. These effects were apparently maintained for up to 5 years, although fewer samples were available as time progressed. No change in other IGF components was observed. Drug and metabolite concentrations were negatively correlated with IGF-I and IGF-I:IGFBP-3 molar ratio in women 50 years of age. Fenretinide induces a moderate decline of IGF-I levels in women 50 years of age. The association between IGF-I change and the reduction of second breast cancers in premenopausal women warrants further study. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.