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01-11-2009 | Epidemiology

The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users

Authors: Monique J. Bijl, Ron H. N. van Schaik, Laureen A. Lammers, Albert Hofman, Arnold G. Vulto, Teun van Gelder, Bruno H. Ch. Stricker, Loes E. Visser

Published in: Breast Cancer Research and Treatment | Issue 1/2009

Abstract

Cytochrome P450 2D6 (CYP2D6) plays an important role in the formation of endoxifen, the active metabolite of tamoxifen. In this study the association between the most prevalent CYP2D6 null-allele in Caucasians (CYP2D6*4) and breast cancer mortality was examined among all incident users of tamoxifen in a population-based cohort study. Breast cancer mortality was significantly increased in patients with the * 4/*4 genotype (HR = 4.1, CI 95% 1.1–15.9, P = 0.041) compared to wild type patients. The breast cancer mortality increased with a hazard ratio of 2.0 (CI 95% 1.1–3.4, P = 0.015) with each additional variant allele. No increased risk of all-cause mortality or all-cancer mortality was found in tamoxifen users carrying a CYP2D6*4 allele. The risk of breast cancer mortality is increased in tamoxifen users with decreased CYP2D6 activity, consistent with the model in which endoxifen formation is dependent on CYP2D6 activity.

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Title: The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users
Authors: Monique J. Bijl
Ron H. N. van Schaik
Laureen A. Lammers
Albert Hofman
Arnold G. Vulto
Teun van Gelder
Bruno H. Ch. Stricker
Loes E. Visser
Publication date: 01-11-2009
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-0272-2

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