Biotransformation of
tamoxifen to the potent
antiestrogen endoxifen is performed by
cytochrome P450 (CYP)
enzymes, in particular the
CYP2D6 isoform.
CYP2D6*4 is one of the most frequent alleles associated with loss of enzymatic activity. The incidence of
CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non-functioning (null) alleles predicts an inferior outcome in postmenopausal women with
breast cancer receiving adjuvant treatment with
tamoxifen. The numerous existing studies investigating the association of
CYP2D6 with treatment failure in
breast cancer are inconsistent and give rather conflicting results. Currently, routine
CYP2D6 testing among women with
breast cancer is not recommended and the significance of
CYP2D6 phenotype in decision making regarding the administration of
tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on
CYP2D6*4, particularly in terms of response to
tamoxifen therapy and
breast cancer outcome.