Cited 81 times since 2009 (4.9 per year) source: EuropePMC Breast cancer research and treatment, Volume 118, Issue 1, 3 1 2009, Pages 125-130 The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users. Bijl MJ, van Schaik RH, Lammers LA, Hofman A, Vulto AG, van Gelder T, Stricker BH, Visser LE
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.
