A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers

A. Decensi, C. Robertson, G. Viale, F. Pigatto, H. Johansson, E.R. Kisanga, P. Veronesi, R. Torrisi, M. Cazzaniga, S. Mora, M.T. Sandri, G. Pelosi, A. Luini, A. Goldhirsch, E.A. Lien, U. Veronesi

Research output: Contribution to journalArticle

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Abstract

Tamoxifen reduces the risk of breast cancer in women at high risk for the disease but increases the risk for endometrial tumors and venous thromboembolisms, possibly in a dose-dependent fashion. We compared the effects of tamoxifen at 1 mg/day and 5 mg/day with those of the standard dose of 20 mg/day on breast cancer proliferation using a surrogate endpoint marker (Ki-67 expression) and blood biomarkers associated with breast cancer, cardiovascular disease, and bone fracture risk. Methods: We randomly assigned 120 women with estrogen receptor (ER)-positive breast cancer to tamoxifen at 1, 5, or 20 mg/day for 4 weeks. Expression of the tumor proliferation marker Ki-67 and of biomarkers of breast cancer (insulin-like growth factor-I, sex hormone-binding globulin), cardiovascular disease (cholesterol, triglycerides, ultrasensitive C-reactive protein, fibrinogen, antithrombin-III), and bone fracture (type I collagen C-telopeptide) risk were determined before (baseline) and after treatment. All levels were compared with those in two nonrandomized control groups (34 women with ER-negative breast cancer and 29 additional women with ER-positive breast cancer). Data were analyzed by analysis of covariance. All statistical tests were two-sided. Expression of Ki-67 decreased in all three tamoxifen groups, with no difference in the magnitude of reduction among groups (P = .81). Relative to baseline, Ki-67 expression decreased by a median of 15.0% (95% confidence interval = 0.0% to 24.1%) among the tamoxifen groups but increased by 12.8% (95% confidence interval = 0.0% to 19.6%) among the nonrandomized control groups. Several blood biomarkers showed dose-response relationships with tamoxifen, including decreased insulin-like growth factor-I, increased sex hormone-binding globulin, and decreased low-density lipoprotein-cholesterol, ultrasensitive C-reactive protein, fibrinogen, and antithrombin-III levels. The effects on Ki-67 expression of lower doses of tamoxifen were comparable to those achieved with the standard dose, although the effects on blood biomarkers were variable. The effects of lower doses of tamoxifen should be assessed further in randomized trials.
LanguageEnglish
Pages779-790
Number of pages11
JournalJournal of the National Cancer Institute
Volume95
Issue number11
DOIs
Publication statusPublished - 2003

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Tamoxifen
Biomarkers
Breast Neoplasms
Estrogen Receptors
Sex Hormone-Binding Globulin
Antithrombin III
Bone Fractures
Insulin-Like Growth Factor I
C-Reactive Protein
Fibrinogen
Cardiovascular Diseases
Confidence Intervals
Control Groups
Venous Thromboembolism
Tumor Biomarkers
Collagen Type I
LDL Cholesterol
Triglycerides
Cholesterol

Keywords

  • cancer
  • tamoxifen
  • breast cancer
  • statistics

Cite this

Decensi, A. ; Robertson, C. ; Viale, G. ; Pigatto, F. ; Johansson, H. ; Kisanga, E.R. ; Veronesi, P. ; Torrisi, R. ; Cazzaniga, M. ; Mora, S. ; Sandri, M.T. ; Pelosi, G. ; Luini, A. ; Goldhirsch, A. ; Lien, E.A. ; Veronesi, U. / A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers. In: Journal of the National Cancer Institute. 2003 ; Vol. 95, No. 11. pp. 779-790.
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Decensi, A, Robertson, C, Viale, G, Pigatto, F, Johansson, H, Kisanga, ER, Veronesi, P, Torrisi, R, Cazzaniga, M, Mora, S, Sandri, MT, Pelosi, G, Luini, A, Goldhirsch, A, Lien, EA & Veronesi, U 2003, 'A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers' Journal of the National Cancer Institute, vol. 95, no. 11, pp. 779-790. https://doi.org/10.1093/jnci/95.11.779

A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers. / Decensi, A.; Robertson, C.; Viale, G.; Pigatto, F.; Johansson, H.; Kisanga, E.R.; Veronesi, P.; Torrisi, R.; Cazzaniga, M.; Mora, S.; Sandri, M.T.; Pelosi, G.; Luini, A.; Goldhirsch, A.; Lien, E.A.; Veronesi, U.

In: Journal of the National Cancer Institute, Vol. 95, No. 11, 2003, p. 779-790.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers

AU - Decensi, A.

AU - Robertson, C.

AU - Viale, G.

AU - Pigatto, F.

AU - Johansson, H.

AU - Kisanga, E.R.

AU - Veronesi, P.

AU - Torrisi, R.

AU - Cazzaniga, M.

AU - Mora, S.

AU - Sandri, M.T.

AU - Pelosi, G.

AU - Luini, A.

AU - Goldhirsch, A.

AU - Lien, E.A.

AU - Veronesi, U.

PY - 2003

Y1 - 2003

N2 - Tamoxifen reduces the risk of breast cancer in women at high risk for the disease but increases the risk for endometrial tumors and venous thromboembolisms, possibly in a dose-dependent fashion. We compared the effects of tamoxifen at 1 mg/day and 5 mg/day with those of the standard dose of 20 mg/day on breast cancer proliferation using a surrogate endpoint marker (Ki-67 expression) and blood biomarkers associated with breast cancer, cardiovascular disease, and bone fracture risk. Methods: We randomly assigned 120 women with estrogen receptor (ER)-positive breast cancer to tamoxifen at 1, 5, or 20 mg/day for 4 weeks. Expression of the tumor proliferation marker Ki-67 and of biomarkers of breast cancer (insulin-like growth factor-I, sex hormone-binding globulin), cardiovascular disease (cholesterol, triglycerides, ultrasensitive C-reactive protein, fibrinogen, antithrombin-III), and bone fracture (type I collagen C-telopeptide) risk were determined before (baseline) and after treatment. All levels were compared with those in two nonrandomized control groups (34 women with ER-negative breast cancer and 29 additional women with ER-positive breast cancer). Data were analyzed by analysis of covariance. All statistical tests were two-sided. Expression of Ki-67 decreased in all three tamoxifen groups, with no difference in the magnitude of reduction among groups (P = .81). Relative to baseline, Ki-67 expression decreased by a median of 15.0% (95% confidence interval = 0.0% to 24.1%) among the tamoxifen groups but increased by 12.8% (95% confidence interval = 0.0% to 19.6%) among the nonrandomized control groups. Several blood biomarkers showed dose-response relationships with tamoxifen, including decreased insulin-like growth factor-I, increased sex hormone-binding globulin, and decreased low-density lipoprotein-cholesterol, ultrasensitive C-reactive protein, fibrinogen, and antithrombin-III levels. The effects on Ki-67 expression of lower doses of tamoxifen were comparable to those achieved with the standard dose, although the effects on blood biomarkers were variable. The effects of lower doses of tamoxifen should be assessed further in randomized trials.

AB - Tamoxifen reduces the risk of breast cancer in women at high risk for the disease but increases the risk for endometrial tumors and venous thromboembolisms, possibly in a dose-dependent fashion. We compared the effects of tamoxifen at 1 mg/day and 5 mg/day with those of the standard dose of 20 mg/day on breast cancer proliferation using a surrogate endpoint marker (Ki-67 expression) and blood biomarkers associated with breast cancer, cardiovascular disease, and bone fracture risk. Methods: We randomly assigned 120 women with estrogen receptor (ER)-positive breast cancer to tamoxifen at 1, 5, or 20 mg/day for 4 weeks. Expression of the tumor proliferation marker Ki-67 and of biomarkers of breast cancer (insulin-like growth factor-I, sex hormone-binding globulin), cardiovascular disease (cholesterol, triglycerides, ultrasensitive C-reactive protein, fibrinogen, antithrombin-III), and bone fracture (type I collagen C-telopeptide) risk were determined before (baseline) and after treatment. All levels were compared with those in two nonrandomized control groups (34 women with ER-negative breast cancer and 29 additional women with ER-positive breast cancer). Data were analyzed by analysis of covariance. All statistical tests were two-sided. Expression of Ki-67 decreased in all three tamoxifen groups, with no difference in the magnitude of reduction among groups (P = .81). Relative to baseline, Ki-67 expression decreased by a median of 15.0% (95% confidence interval = 0.0% to 24.1%) among the tamoxifen groups but increased by 12.8% (95% confidence interval = 0.0% to 19.6%) among the nonrandomized control groups. Several blood biomarkers showed dose-response relationships with tamoxifen, including decreased insulin-like growth factor-I, increased sex hormone-binding globulin, and decreased low-density lipoprotein-cholesterol, ultrasensitive C-reactive protein, fibrinogen, and antithrombin-III levels. The effects on Ki-67 expression of lower doses of tamoxifen were comparable to those achieved with the standard dose, although the effects on blood biomarkers were variable. The effects of lower doses of tamoxifen should be assessed further in randomized trials.

KW - cancer

KW - tamoxifen

KW - breast cancer

KW - statistics

UR - http://dx.doi.org/10.1093/jnci/95.11.779

U2 - 10.1093/jnci/95.11.779

DO - 10.1093/jnci/95.11.779

M3 - Article

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SP - 779

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JO - Journal of the National Cancer Institute

T2 - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

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ER -