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BMC Cancer
Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | Research article

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

Authors: Jennifer Gjerde, Jürgen Geisler, Steinar Lundgren, Dagfinn Ekse, Jan Erik Varhaug, Gunnar Mellgren, Vidar M Steen, Ernst A Lien

Published in: BMC Cancer | Issue 1/2010

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Abstract

Background

The 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.

Methods

Tamoxifen 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.

Results

We 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.

Conclusions

We 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.
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Metadata
Title
Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer
Authors
Jennifer Gjerde
Jürgen Geisler
Steinar Lundgren
Dagfinn Ekse
Jan Erik Varhaug
Gunnar Mellgren
Vidar M Steen
Ernst A Lien
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-313

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