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Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women

The use of tamoxifen as a preventive agent may be limited by the increased risk of endometrial cancer and venous thromboembolic events observed in postmenopausal women. We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease... Full description

Journal Title: Breast cancer research and treatment 2001, Vol.69 (1), p.21-27
Main Author: BONANNI, Bernardo
Other Authors: JOHANSSON, Harriet , DECENSI, Andrea , GANDINI, Sara , GUERRIERI-GONZAGA, Aliana , TORRISI, Rosalba , SANDRI, Maria Teresa , CAZZANIGA, Massimiliano , MORA, Serena , ROBERTSON, Chris , LIEN, Ernst Asbjorn
Format: Electronic Article Electronic Article
Language: English
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Publisher: Dordrecht: Springer
ID: ISSN: 0167-6806
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title: Effect of low dose tamoxifen on the insulin-like growth factor system in healthy women
format: Article
creator:
  • BONANNI, Bernardo
  • JOHANSSON, Harriet
  • DECENSI, Andrea
  • GANDINI, Sara
  • GUERRIERI-GONZAGA, Aliana
  • TORRISI, Rosalba
  • SANDRI, Maria Teresa
  • CAZZANIGA, Massimiliano
  • MORA, Serena
  • ROBERTSON, Chris
  • LIEN, Ernst Asbjorn
subjects:
  • Anticarcinogenic Agents - administration & dosage
  • Anticarcinogenic Agents - pharmacology
  • Antineoplastic agents
  • Biological and medical sciences
  • Biomarkers, Tumor - analysis
  • Breast Neoplasms - prevention & control
  • Dose-Response Relationship, Drug
  • Female
  • General aspects
  • Humans
  • Insulin-Like Growth Factor I - analysis
  • Insulin-Like Growth Factor I - biosynthesis
  • Medical sciences
  • Middle Aged
  • Pharmacology. Drug treatments
  • Placebos
  • Tamoxifen - administration & dosage
  • Tamoxifen - pharmacology
ispartof: Breast cancer research and treatment, 2001, Vol.69 (1), p.21-27
description: The use of tamoxifen as a preventive agent may be limited by the increased risk of endometrial cancer and venous thromboembolic events observed in postmenopausal women. We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease and breast cancer, including Insulin-like Growth Factor-I (IGF-I). To provide further insight into the effect of tamoxifen at low doses on the IGF system, we have correlated the drug serum levels attained after 2 months of either placebo (n = 32), tamoxifen 20 mg/day (n = 26), 10 mg/day (n = 23) or 10 mg/every other day (n = 29) with the changes in IGF-I, Insulin-like Growth Factor-II (IGF-II), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), and IGF-I/IGFBP-3 ratio. Compared with placebo, tamoxifen induced a mean +/- standard error (SE) reduction of IGF-I of 16.9 +/- 7.8%, p < 0.05, a non-significant increase of 22.9 +/- 12.2% in IGF-II, an increase in IGFBP-1 of 49.3 +/- 22.7%, p < 0.05, and a non-significant change of IGFBP-3 (-4.0% +/- 9.2). No significant concentration-response relationship was observed between serum tamoxifen concentrations and the biomarker changes except for the ratio of IGF-I/IGFBP-3, which decreased by 1.53 +/- 0.68% for any increase by 10 ng/ml of serum tamoxifen concentration (p = 0.02). Although low tamoxifen concentrations induce a comparable modulation of the IGF family relative to the conventional dose, the lower decrements in the IGF-I/IGFBP-3 ratio observed at low drug concentrations might be associated with a reduced preventive activity. Further studies on the search of the minimal active dose of tamoxifen are warranted.
language: eng
source:
identifier: ISSN: 0167-6806
fulltext: no_fulltext
issn:
  • 0167-6806
  • 1573-7217
url: Link


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titleEffect of low dose tamoxifen on the insulin-like growth factor system in healthy women
creatorBONANNI, Bernardo ; JOHANSSON, Harriet ; DECENSI, Andrea ; GANDINI, Sara ; GUERRIERI-GONZAGA, Aliana ; TORRISI, Rosalba ; SANDRI, Maria Teresa ; CAZZANIGA, Massimiliano ; MORA, Serena ; ROBERTSON, Chris ; LIEN, Ernst Asbjorn
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descriptionThe use of tamoxifen as a preventive agent may be limited by the increased risk of endometrial cancer and venous thromboembolic events observed in postmenopausal women. We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease and breast cancer, including Insulin-like Growth Factor-I (IGF-I). To provide further insight into the effect of tamoxifen at low doses on the IGF system, we have correlated the drug serum levels attained after 2 months of either placebo (n = 32), tamoxifen 20 mg/day (n = 26), 10 mg/day (n = 23) or 10 mg/every other day (n = 29) with the changes in IGF-I, Insulin-like Growth Factor-II (IGF-II), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), and IGF-I/IGFBP-3 ratio. Compared with placebo, tamoxifen induced a mean +/- standard error (SE) reduction of IGF-I of 16.9 +/- 7.8%, p < 0.05, a non-significant increase of 22.9 +/- 12.2% in IGF-II, an increase in IGFBP-1 of 49.3 +/- 22.7%, p < 0.05, and a non-significant change of IGFBP-3 (-4.0% +/- 9.2). No significant concentration-response relationship was observed between serum tamoxifen concentrations and the biomarker changes except for the ratio of IGF-I/IGFBP-3, which decreased by 1.53 +/- 0.68% for any increase by 10 ng/ml of serum tamoxifen concentration (p = 0.02). Although low tamoxifen concentrations induce a comparable modulation of the IGF family relative to the conventional dose, the lower decrements in the IGF-I/IGFBP-3 ratio observed at low drug concentrations might be associated with a reduced preventive activity. Further studies on the search of the minimal active dose of tamoxifen are warranted.
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subjectAnticarcinogenic Agents - administration & dosage ; Anticarcinogenic Agents - pharmacology ; Antineoplastic agents ; Biological and medical sciences ; Biomarkers, Tumor - analysis ; Breast Neoplasms - prevention & control ; Dose-Response Relationship, Drug ; Female ; General aspects ; Humans ; Insulin-Like Growth Factor I - analysis ; Insulin-Like Growth Factor I - biosynthesis ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Placebos ; Tamoxifen - administration & dosage ; Tamoxifen - pharmacology
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1JOHANSSON, Harriet
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3GANDINI, Sara
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5TORRISI, Rosalba
6SANDRI, Maria Teresa
7CAZZANIGA, Massimiliano
8MORA, Serena
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descriptionThe use of tamoxifen as a preventive agent may be limited by the increased risk of endometrial cancer and venous thromboembolic events observed in postmenopausal women. We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease and breast cancer, including Insulin-like Growth Factor-I (IGF-I). To provide further insight into the effect of tamoxifen at low doses on the IGF system, we have correlated the drug serum levels attained after 2 months of either placebo (n = 32), tamoxifen 20 mg/day (n = 26), 10 mg/day (n = 23) or 10 mg/every other day (n = 29) with the changes in IGF-I, Insulin-like Growth Factor-II (IGF-II), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), and IGF-I/IGFBP-3 ratio. Compared with placebo, tamoxifen induced a mean +/- standard error (SE) reduction of IGF-I of 16.9 +/- 7.8%, p < 0.05, a non-significant increase of 22.9 +/- 12.2% in IGF-II, an increase in IGFBP-1 of 49.3 +/- 22.7%, p < 0.05, and a non-significant change of IGFBP-3 (-4.0% +/- 9.2). No significant concentration-response relationship was observed between serum tamoxifen concentrations and the biomarker changes except for the ratio of IGF-I/IGFBP-3, which decreased by 1.53 +/- 0.68% for any increase by 10 ng/ml of serum tamoxifen concentration (p = 0.02). Although low tamoxifen concentrations induce a comparable modulation of the IGF family relative to the conventional dose, the lower decrements in the IGF-I/IGFBP-3 ratio observed at low drug concentrations might be associated with a reduced preventive activity. Further studies on the search of the minimal active dose of tamoxifen are warranted.
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4Biomarkers, Tumor - analysis
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6Dose-Response Relationship, Drug
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10Insulin-Like Growth Factor I - analysis
11Insulin-Like Growth Factor I - biosynthesis
12Medical sciences
13Middle Aged
14Pharmacology. Drug treatments
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16Tamoxifen - administration & dosage
17Tamoxifen - pharmacology
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titleEffect of low dose tamoxifen on the insulin-like growth factor system in healthy women
authorBONANNI, Bernardo ; JOHANSSON, Harriet ; DECENSI, Andrea ; GANDINI, Sara ; GUERRIERI-GONZAGA, Aliana ; TORRISI, Rosalba ; SANDRI, Maria Teresa ; CAZZANIGA, Massimiliano ; MORA, Serena ; ROBERTSON, Chris ; LIEN, Ernst Asbjorn
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1Anticarcinogenic Agents - pharmacology
2Antineoplastic agents
3Biological and medical sciences
4Biomarkers, Tumor - analysis
5Breast Neoplasms - prevention & control
6Dose-Response Relationship, Drug
7Female
8General aspects
9Humans
10Insulin-Like Growth Factor I - analysis
11Insulin-Like Growth Factor I - biosynthesis
12Medical sciences
13Middle Aged
14Pharmacology. Drug treatments
15Placebos
16Tamoxifen - administration & dosage
17Tamoxifen - pharmacology
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1JOHANSSON, Harriet
2DECENSI, Andrea
3GANDINI, Sara
4GUERRIERI-GONZAGA, Aliana
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6SANDRI, Maria Teresa
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jtitleBreast cancer research and treatment
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abstractThe use of tamoxifen as a preventive agent may be limited by the increased risk of endometrial cancer and venous thromboembolic events observed in postmenopausal women. We have recently shown a comparable activity of lower doses of tamoxifen on several surrogate biomarkers of cardiovascular disease and breast cancer, including Insulin-like Growth Factor-I (IGF-I). To provide further insight into the effect of tamoxifen at low doses on the IGF system, we have correlated the drug serum levels attained after 2 months of either placebo (n = 32), tamoxifen 20 mg/day (n = 26), 10 mg/day (n = 23) or 10 mg/every other day (n = 29) with the changes in IGF-I, Insulin-like Growth Factor-II (IGF-II), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1), Insulin-like Growth Factor Binding Protein-3 (IGFBP-3), and IGF-I/IGFBP-3 ratio. Compared with placebo, tamoxifen induced a mean +/- standard error (SE) reduction of IGF-I of 16.9 +/- 7.8%, p < 0.05, a non-significant increase of 22.9 +/- 12.2% in IGF-II, an increase in IGFBP-1 of 49.3 +/- 22.7%, p < 0.05, and a non-significant change of IGFBP-3 (-4.0% +/- 9.2). No significant concentration-response relationship was observed between serum tamoxifen concentrations and the biomarker changes except for the ratio of IGF-I/IGFBP-3, which decreased by 1.53 +/- 0.68% for any increase by 10 ng/ml of serum tamoxifen concentration (p = 0.02). Although low tamoxifen concentrations induce a comparable modulation of the IGF family relative to the conventional dose, the lower decrements in the IGF-I/IGFBP-3 ratio observed at low drug concentrations might be associated with a reduced preventive activity. Further studies on the search of the minimal active dose of tamoxifen are warranted.
copDordrecht
pubSpringer
pmid11759825
doi10.1023/A:1012241505717