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Tamoxifen and metabolite concentrations in serum and breast cancer tissue during three dose regimens in a randomized preoperative trial

Kisanga, E.R. and Gjerde, J. and Guerrieri-Gonzaga, A. and Pigatto, F. and Pesci-Feltri, A. and Robertson, C. and Serrano, D. and Pelosi, G. (2004) Tamoxifen and metabolite concentrations in serum and breast cancer tissue during three dose regimens in a randomized preoperative trial. Clinical Cancer Research, 10 (7). pp. 2336-2343. ISSN 1557-3265

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Abstract

Purpose: Both therapeutic and adverse effects of tamoxifen may be related to its tissue concentrations. We investigated concentrations of tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, and N-didesmethyltamoxifen in serum, normal breast, and breast cancer tissues during conventional dosage and two low-dose regimens. Furthermore we studied tamoxifen effects on the cancer proliferation marker Ki-67, and on sex hormone-binding globulin (SHBG). Experimental Design: From September 1999 to August 2001, 120 breast cancer patients were randomized to 20-, 5-, or 1-mg tamoxifen daily. We measured serum and tissue concentrations of tamoxifen and three metabolites after 28 days of treatment, and the changes between baseline and post-treatment levels of SHBG and Ki-67. Results: The median (range) tamoxifen concentrations (ng/ml) at doses of 1, 5, and 20 mg daily (n = 38, 37, and 36) were 7.5 (2.9-120.9), 25.2 (1.9-180.9), and 83.6 (8.7-134.4) in serum, and 78.2 (35.9-184), 272.3 (122-641), and 744.4 (208.6-2556) in breast cancer tissue, respectively. Tamoxifen levels followed a dose-concentration relationship. The concentrations of tamoxifen and metabolites were related to each other. Serum and tissue concentrations of tamoxifen were associated with corresponding changes of SHBG levels, whereas changes of Ki-67 levels were not related. Conclusions: Estrogen agonistic effects of tamoxifen on SHBG decreased with lower dosage, whereas tamoxifen effects on Ki-67 expression did not change. This together with a >10-fold variation in serum tamoxifen concentrations and a serum to tissue concentration relationship suggest that tamoxifen treatment may be improved by administration of lower doses and therapeutic drug monitoring.

Item type: Article
ID code: 17335
Notes: Strathprints' policy is to record up to 8 authors per publication, plus any additional authors based at the University of Strathclyde. More authors may be listed on the official publication than appear in the Strathprints' record.
Keywords: Tamoxifen, Metabolite, breast cancer tissue, dose regimens, preoperative trial, cancer, Neoplasms. Tumors. Oncology (including Cancer), Statistics, Cancer Research, Oncology
Subjects: Medicine > Internal medicine > Neoplasms. Tumors. Oncology (including Cancer)
Social Sciences > Statistics
Department: Faculty of Science > Mathematics and Statistics
Related URLs:
    Depositing user: Strathprints Administrator
    Date Deposited: 26 Apr 2010 16:31
    Last modified: 05 Sep 2014 01:22
    URI: http://strathprints.strath.ac.uk/id/eprint/17335

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