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 language | English |
|---|---|
| Pages (from-to) | 4722-4729 |
| Number of pages | 8 |
| Journal | Clinical Cancer Research |
| Volume | 9 |
| Issue number | 13 |
| Publication status | Published - Oct 15 2003 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
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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UR - http://www.scopus.com/inward/citedby.url?scp=10744228790&partnerID=8YFLogxK
M3 - Article
C2 - 14581342
AN - SCOPUS:10744228790
VL - 9
SP - 4722
EP - 4729
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 13
ER -