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

Monique Bijl; Ron van Schaik; LA Lammers; Bert Hofman; Arnold Vulto; Teun Gelder; Bruno Stricker; Loes Visser

doi:10.1007/s10549-008-0272-2

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

Monique Bijl, Ron van Schaik, LA Lammers, Bert Hofman, Arnold Vulto, Teun Gelder, Bruno Stricker, Loes Visser

Research output: Contribution to journal › Article › Academic › peer-review

112 Citations (Scopus)

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.

Original language	Undefined/Unknown
Pages (from-to)	125-130
Number of pages	6
Journal	Breast Cancer Research and Treatment
Volume	118
Issue number	1
DOIs	https://doi.org/10.1007/s10549-008-0272-2
Publication status	Published - 2009

Research programs

EMC NIHES-01-64-03
EMC NIHES-03-77-02
EMC OR-01-25-01
EMC OR-01-34-01

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s10549-008-0272-2

http://hdl.handle.net/1765/24205

Cite this

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title = "The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users",

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.",

author = "Monique Bijl and {van Schaik}, Ron and LA Lammers and Bert Hofman and Arnold Vulto and Teun Gelder and Bruno Stricker and Loes Visser",

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T1 - The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users

AU - Bijl, Monique

AU - van Schaik, Ron

AU - Lammers, LA

AU - Hofman, Bert

AU - Vulto, Arnold

AU - Gelder, Teun

AU - Stricker, Bruno

AU - Visser, Loes

PY - 2009

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N2 - 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.

AB - 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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