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

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dc.contributor.author Gjerde, Jennifer eng
dc.contributor.author Geisler, Jürgen eng
dc.contributor.author Lundgren, Steinar eng
dc.contributor.author Ekse, Dagfinn eng
dc.contributor.author Varhaug, Jan Erik eng
dc.contributor.author Mellgren, Gunnar eng
dc.contributor.author Steen, Vidar Martin eng
dc.contributor.author Lien, Ernst Asbjørn eng
dc.date.accessioned 2011-04-19T07:32:49Z
dc.date.available 2011-04-19T07:32:49Z
dc.date.issued 2010-06-21 eng
dc.identifier.citation BMC Cancer 10:313 en_US
dc.identifier.issn 1471-2407 eng
dc.identifier.uri http://hdl.handle.net/1956/4673
dc.description.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. en_US
dc.language.iso eng eng
dc.publisher BioMed Central eng
dc.rights Attribution CC BY eng
dc.rights.uri http://creativecommons.org/licenses/by/2.0 eng
dc.title Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer eng
dc.type Peer reviewed eng
dc.type Journal article eng
dc.subject.nsi VDP::Medical disciplines: 700 eng
dc.rights.holder Copyright 2010 Gjerde et al; licensee BioMed Central Ltd.
dc.rights.holder Gjerde et al. eng
dc.type.version publishedVersion eng
bora.peerreviewed Peer reviewed eng
bora.cristinID 347983 eng
bibo.doi http://dx.doi.org/10.1186/1471-2407-10-313 eng
dc.identifier.cristinID 347983 eng
dc.identifier.doi http://dx.doi.org/10.1186/1471-2407-10-313


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