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Title: Prevalent breast cancer patients with a homozygous mutant status for CYP2D6*4: response and biomarkers in tamoxifen users
Authors: Dieudonné, A ×
Lambrechts, Diether
Claes, Bart
Vandorpe, Thijs
Wildiers, Hans
Timmerman, Dirk
Billen, Jaak
Leunen, K
Amant, Frédéric
Berteloot, Patrick
Smeets, Ann
Paridaens, Robert
Weltens, Caroline
Van Limbergen, Erik
Van den Bogaert, Walter
Vergote, Ignace
Van Huffel, Sabine
Christiaens, Marie-Rose
Neven, Patrick #
Issue Date: Dec-2009
Publisher: M. Nijhoff
Series Title: Breast Cancer Research and Treatment vol:118 issue:3 pages:531-538
Abstract: Retrospective studies suggest that single nucleotide polymorphisms in the cytochrome P450 2D6 (CYP2D6) gene predict reduced tamoxifen metabolism, better tolerance and worse treatment outcome. We hypothesized that women with this genotype lack tamoxifen-induced endometrial and biochemical changes in follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG). We identified 56 breast cancer patients attending the follow-up clinic with a homozygous mutant (HM) status for the CYP2D6*4 null variant. Here, we report a detailed assessment of tamoxifen activity in 19 CYP2D6 HM women, while they were using tamoxifen either for metastatic (n = 5) or for early disease (n = 14). We assessed response to tamoxifen in metastatic disease. Endometrial appearances and serum levels of FSH and SHBG were assessed from retrospective and prospective testing. Our findings do suggest that the presence of two CYP2D6*4 alleles does not exclude a durable response of tamoxifen in metastatic breast cancer. The transvaginal ultrasonographic appearance of the endometrium in CYP2D6*4/*4 patients on tamoxifen is similar as seen in the normal population of tamoxifen users. The endometrium is increased in thickness with subepithelial cysts and endometrial polyps. Serum levels of FSH and SHBG in CYP2D6*4 HM tamoxifen users were in the range of what would be expected during tamoxifen treatment in the general population. Our findings do show CYP2D6*4/*4 carriers to have activity of tamoxifen on breast cancer, endometrium and serum levels of FSH and SHBG. They support clinical trials prospectively testing the effect of CYP2D6 genetic variability in response to tamoxifen before denying this drug to breast cancer patients only based on their CYP2D6*4 status.
URI: 
ISSN: 0167-6806
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Gynaecological Oncology
Vesalius Research Centre (-)
Laboratory of Experimental Oncology
Gynaecological Imaging Section (-)
Section Woman - Miscellaneous (-)
Laboratory of Experimental Radiotherapy
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Multidisciplinary Breast Clinic Section (-)
Surgical Oncology
Laboratory of Translational Genetics (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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