Strathprints Home | Open Access | Browse | Search | User area | Copyright | Help | Library Home | SUPrimo

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

Decensi, A. and Robertson, C. and Viale, G. and Pigatto, F. and Johansson, H. and Kisanga, E.R. and Veronesi, P. and Torrisi, R. and Cazzaniga, M. and Mora, S. and Sandri, M.T. and Pelosi, G. and Luini, A. and Goldhirsch, A. and Lien, E.A. and Veronesi, U. (2003) A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers. Journal of the National Cancer Institute, 95 (11). pp. 779-790. ISSN 0027-8874

Full text not available in this repository. (Request a copy from the Strathclyde author)

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.

Item type: Article
ID code: 4596
Keywords: cancer, tamoxifen, breast cancer, statistics, Probabilities. Mathematical statistics, Neoplasms. Tumors. Oncology (including Cancer), Public health. Hygiene. Preventive Medicine, Cancer Research, Oncology
Subjects: Science > Mathematics > Probabilities. Mathematical statistics
Medicine > Internal medicine > Neoplasms. Tumors. Oncology (including Cancer)
Medicine > Public aspects of medicine > Public health. Hygiene. Preventive Medicine
Department: Faculty of Science > Mathematics and Statistics
Unknown Department
Related URLs:
    Depositing user: Strathprints Administrator
    Date Deposited: 06 Nov 2007
    Last modified: 04 Sep 2014 15:21
    URI: http://strathprints.strath.ac.uk/id/eprint/4596

    Actions (login required)

    View Item