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




Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Cancer

, 10:313

First Online: 21 June 2010Received: 11 February 2010Accepted: 21 June 2010DOI: 10.1186-1471-2407-10-313

Cite this article as: Gjerde, J., Geisler, J., Lundgren, S. et al. BMC Cancer 2010 10: 313. doi:10.1186-1471-2407-10-313

Abstract

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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-10-313 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Autor: Jennifer Gjerde - Jürgen Geisler - Steinar Lundgren - Dagfinn Ekse - Jan Erik Varhaug - Gunnar Mellgren - Vidar M Steen

Fuente: https://link.springer.com/







Documentos relacionados