Molecular Oncology, Markers, Clinical Correlates Relationships between Plasma Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Protein-3 and Second Breast Cancer Risk in a Prevention Trial of Fenretinide Andrea Decensi1, Umberto Veronesi, Rosalba Miceli, Harriet Johansson, Luigi Mariani, Tiziana Camerini, Maria Gaetana Di Mauro, Elena Cavadini, Giuseppe De Palo, Alberto Costa, Marjorie Perloff, Winfred F. Malone and Franca Formelli Divisions of Chemoprevention [A. D., H. J.], Breast Surgery [U. V.], and Laboratory Medicine [H. J.], European Institute of Oncology, Milan 20141, Italy; Units of Medical Statistics and Biometry [L. M., R. M.], Chemoprevention [E. C., F. F.], Scientific Director’s Office [T. C.], and Preventive Medicine [M. G. D. M., G. D. P.], Istituto Nazionale Tumori, 20133 Milan, Italy; Division of Breast Surgery, Fondazione Maugeri, 27100 Pavia, Italy [A. C.]; and Chemoprevention Agent Development Research Group, National Cancer Institute, Bethesda, Maryland 20852 [M. P., W. F. M.] ABSTRACT Purpose: High circulating insulin-like growth factor (IGF) -I and/or low IGF-binding protein (IGFBP) -3 levels are associated with increased breast cancer risk in unaffected premenopausal women. We determined whether IGF-I and IGFBP-3 predict second breast cancer risk, and whether their changes during fenretinide explain observed reductions in second breast cancer in women 50 years of age. Experimental Design: Within a Phase III trial, we measured baseline and 1-year levels of IGF-I, IGFBP-3, and their ratio in 302 subjects on fenretinide and 220 controls who provided plasma samples. The prognostic effect of IGF-I and IGFBP-3, and the surrogate effect of IGF-I during fenretinide were assessed by Cox models after 9.4 years. Results: Among controls, high IGF-I and low IGFBP-3 were associated with elevated second breast cancer risk [top versus bottom tertile, IGF-I, hazard ratio (HR) = 1.94, 95% confidence interval (CI), 0.87–4.31, P = 0.105; and IGFBP-3, HR = 0.40, 95% CI, 0.18–0.93, P = 0.033]. Fenretinide induced reductions of IGF-I, IGFBP-3, and IGF-I:IGFBP-3 of 8% (95% CI, 2–12%; P = 0.004), 3% (95% CI, 1–5%; P = 0.002), and 5% (95% CI, 0–10%; P = 0.050), respectively. Second breast cancer risk was reduced by 39% (HR = 0.61; 95% CI, 0.40–0.94; P = 0.026). The percentage of treatment effect explained by IGF-I and IGF-I:IGFBP-3 reductions were 4.8% (95% CI, 0.8–28.9%) and 3.1% (95% CI, 0.5–20.8%), respectively. Conclusions: Fenretinide induced a moderate reduction of IGF-I, which marginally explains observed cancer risk reductions in women "low IGFBP-3 levels predict second breast cancer risk. Clinical Cancer Research Vol. 9, 4722-4729, October 15, 2003 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.