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

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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

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Fenretinide
Insulin-Like Growth Factor Binding Protein 3
Second Primary Neoplasms
Insulin-Like Growth Factor I
Breast Neoplasms
Confidence Intervals
Risk Reduction Behavior
Proportional Hazards Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / Decensi, Andrea; Veronesi, Umberto; Miceli, Rosalba; Johansson, Harriet; Mariani, Luigi; Camerini, Tiziana; Di Mauro, Maria Gaetana; Cavadini, Elena; De Palo, Giuseppe; Costa, Alberto; Perloff, Marjorie; Malone, Winfred F.; Formelli, Franca.

In: Clinical Cancer Research, Vol. 9, No. 13, 15.10.2003, p. 4722-4729.

Research output: Contribution to journalArticle

Decensi, Andrea ; Veronesi, Umberto ; Miceli, Rosalba ; Johansson, Harriet ; Mariani, Luigi ; Camerini, Tiziana ; Di Mauro, Maria Gaetana ; Cavadini, Elena ; De Palo, Giuseppe ; Costa, Alberto ; Perloff, Marjorie ; Malone, Winfred F. ; Formelli, Franca. / 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. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 13. pp. 4722-4729.
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title = "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",
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.",
author = "Andrea Decensi and Umberto Veronesi and Rosalba Miceli and Harriet Johansson and Luigi Mariani and Tiziana Camerini and {Di Mauro}, {Maria Gaetana} and Elena Cavadini and {De Palo}, Giuseppe and Alberto Costa and Marjorie Perloff and Malone, {Winfred F.} and Franca Formelli",
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T1 - 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

AU - Decensi, Andrea

AU - Veronesi, Umberto

AU - Miceli, Rosalba

AU - Johansson, Harriet

AU - Mariani, Luigi

AU - Camerini, Tiziana

AU - Di Mauro, Maria Gaetana

AU - Cavadini, Elena

AU - De Palo, Giuseppe

AU - Costa, Alberto

AU - Perloff, Marjorie

AU - Malone, Winfred F.

AU - Formelli, Franca

PY - 2003/10/15

Y1 - 2003/10/15

N2 - 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.

AB - 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.

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