Long-term effects of fenretinide, a retinoic acid derivative, on the insulin-like growth factor system in women with early breast cancer

A. Decensi, H. Johansson, R. Miceli, L. Mariani, T. Camerini, E. Cavadini, M. G. Di Mauro, A. Barreca, A. G. Gonzaga, S. Diani, M. T. Sandri, G. De Palo, F. Formelli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1047-1053
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume10
Issue number10
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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