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 Decensi, 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, Franca Formelli

Research output: Contribution to journalArticlepeer-review

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 ≤50 years of age. In this age group high IGF-I and particularly low IGFBP-3 levels predict second breast cancer risk.

Original languageEnglish
Pages (from-to)4722-4729
Number of pages8
JournalClinical Cancer Research
Volume9
Issue number13
Publication statusPublished - Oct 15 2003

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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