Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer

BMC Cancer

Research Article

Dagfinn Ekse¹  Jürgen Geisler²  Steinar Lundgren³  Jan Erik Varhaug⁴  Vidar M Steen⁵  Ernst A Lien⁶  Gunnar Mellgren⁶  Jennifer Gjerde⁶ 

[1] Department of Oncology, Haukeland University Hospital, N-5021, Bergen, Norway;Department of Oncology, Haukeland University Hospital, N-5021, Bergen, Norway;Section for Oncology, Institute of Medicine, University of Bergen, N-5021, Bergen, Norway;Section of Oncology, Department of Medicine, Akershus University Hospital, N-1478, Lørenskog, Norway;Department of Oncology, St. Olavs University Hospital, N-7006, Trondheim, Norway;Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N-7006, Trondheim, Norway;Department of Surgery, Haukeland University Hospital, N-5021, Bergen, Norway;Department of Surgical Sciences, University of Bergen, N-5021, Bergen, Norway;Dr. E. Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, N-5021, Bergen, Norway;Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, N-5021, Bergen, Norway;Faculty Division Akerhus University Hospital, University of Oslo, N-0316, Oslo, Norway;Hormone Laboratory, Haukeland University Hospital, N-5021, Bergen, Norway;Section for Endocrinology, Institute of Medicine, University of Bergen, N-5021, Bergen, Norway;

关键词: Tamoxifen;    DHEA;    Poor Metaboliser;    Tamoxifen Treatment;    Metabolic Ratio;   

DOI  :  10.1186/1471-2407-10-313

 received in 2010-02-11, accepted in 2010-06-21,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe cytochrome P450 (CYP) enzymes 2C19, 2D6, and 3A5 are responsible for converting the selective estrogen receptor modulator (SERM), tamoxifen to its active metabolites 4-hydroxy-tamoxifen (4OHtam) and 4-hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen). Inter-individual variations of the activity of these enzymes due to polymorphisms may be predictors of outcome of breast cancer patients during tamoxifen treatment. Since tamoxifen and estrogens are both partly metabolized by these enzymes we hypothesize that a correlation between serum tamoxifen and estrogen levels exists, which in turn may interact with tamoxifen on treatment outcome. Here we examined relationships between the serum levels of tamoxifen, estrogens, follicle-stimulating hormone (FSH), and also determined the genotypes of CYP2C19, 2D6, 3A5, and SULT1A1 in 90 postmenopausal breast cancer patients.MethodsTamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Estrogen and FSH levels were determined using a sensitive radio- and chemiluminescent immunoassay, respectively.ResultsWe observed significant correlations between the serum concentrations of tamoxifen, N-dedimethyltamoxifen, and tamoxifen-N-oxide and estrogens (p < 0.05). The genotype predicted CYP2C19 activity influenced the levels of both tamoxifen metabolites and E1.ConclusionsWe have shown an association between tamoxifen and its metabolites and estrogen serum levels. An impact of CYP2C19 predicted activity on tamoxifen, as well as estrogen kinetics may partly explain the observed association between tamoxifen and its metabolites and estrogen serum levels. Since the role of estrogen levels during tamoxifen therapy is still a matter of debate further prospective studies to examine the effect of tamoxifen and estrogen kinetics on treatment outcome are warranted.

【 授权许可】

Unknown   
© Gjerde et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.