JNCI Commentary (open access): CYP2D6 Genotype as a Marker for Benefit of Adjuvant Tamoxifen in Postmenopausal Women: Lessons Learned

Blogger's Note: see extensive references including current papers regarding this issue

 "Since 2003, there has been considerable interest and a good degree of credence given to the role of cytochrome P450 2D6 (CYP2D6) genotyping to predict tamoxifen benefit in adjuvant therapy (1–5). This construct was based on the fact that a variety of CYP2D6 polymorphisms lead to reduced CYP2D6 enzyme activity and hence result in lower plasma concentrations of endoxifen, a clinically active metabolite of tamoxifen.....


"In the end, it is crucial to obtain data from randomized trials for clinical demonstration of associations between biomarkers and disease outcomes. To advance breast cancer therapy, laboratory observations that raise hypotheses must be at the very core of what we do; however, it is only after independent validation that they can begin guide clinical practice."

1. 15.↵
   1. Regan MM,
   2. Leyland-Jones B,
   3. Bouzyk M,
   4. et al

   . CYP2D6 genotype and tamoxifen response in postmenopausal women with estrogen-responsive early breast cancer: the Breast International Group 1-98 Trial. J Natl Cancer Inst. 2012;104(6):441-451.
2. 16.↵
   1. Rae JM,
   2. Drury S,
   3. Hayes DF,
   4. et al

   . CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst. 2012;104(6):452-460.