The CYP2D6 4 polymorphism affects breast cancer survival in tamoxifen users
Breast Cancer Research and Treatment , Volume 118 - Issue 1 p. 125- 130
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 (CYP2D64) 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 CYP2D64 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.
|Breast cancer, CYP2D6, Polymorphism, Tamoxifen|
|Breast Cancer Research and Treatment|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Bijl, M.J, van Schaik, R.H.N, Lammers, L.A, Hofman, A, Vulto, A.G, van Gelder, T, … Visser, L.E. (2009). The CYP2D6 4 polymorphism affects breast cancer survival in tamoxifen users. Breast Cancer Research and Treatment, 118(1), 125–130. doi:10.1007/s10549-008-0272-2