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.

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doi.org/10.1007/s10549-008-0272-2, hdl.handle.net/1765/24205
Breast Cancer Research and Treatment
Erasmus MC: University Medical Center Rotterdam

Bijl, M., van Schaik, R., Lammers, L., Hofman, A., Vulto, A., van Gelder, T., … Visser, L. (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