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

Monique J. Bijl (1, 2) , Ron H. N. Schaik (3) , Laureen A. Lammers (2) , Albert Hofman (1) , Arnold G. Vulto (2) , Teun Gelder (2, 4) , Bruno H. Ch. Stricker (1, 4, 5) , Loes E. Visser (1, 2)

1 Department of Epidemiology
2 Department of Hospital Pharmacy
3 Department of Clinical Chemistry
4 Department of Internal Medicine
5 Drug Safety Unit

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 () 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 genotype (HR = 4.1, CI 95% 1.1–15.9,  = 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,  = 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 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.

Mots clés: CYP2D6*4; Polymorphism; Tamoxifen; Breast cancer

Monique J. Bijl, Ron H. N. Schaik, Laureen A. Lammers, Albert Hofman, Arnold G. Vulto, et al.. The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users. Breast Cancer Research and Treatment, 2009, 118 (1), pp.125-130. ⟨10.1007/s10549-008-0272-2⟩. ⟨hal-00535322⟩