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1. Oncologist. 2012 Apr 24. [Epub ahead of print]

Tamoxifen and CYP2D6: A Contradiction of Data.

Hertz DL, McLeod HL, Irvin WJ Jr.

Division of Pharmacotherapy and Experimental Therapeutics.

AbstractTamoxifen is an effective antiestrogen used in the treatment of hormone
receptor-positive breast cancer. Bioconversion of tamoxifen to endoxifen, its
most abundant active metabolite, is primarily dependent on the activity of
cytochrome P450 2D6 (CYP2D6), which is highly polymorphic. Over 20 published
studies have reported on the potential association between CYP2D6 polymorphism
and tamoxifen treatment outcome, with highly inconsistent results. The purpose of
this review is to explore differences among 17 independent studies to identify
factors that may have contributed to the discrepant findings. This report
discusses six putative factors that are grouped into two categories: (a) clinical
management criteria: hormone receptor classification, menopausal status, and
tamoxifen combination therapy; (b) pharmacologic criteria: genotyping
comprehensiveness, CYP2D6 inhibitor coadministration, and tamoxifen adherence.
Comparison of these factors between the positive and negative studies suggests
that tamoxifen combination therapy, genotyping comprehensiveness, and CYP2D6
inhibitor coadministration may account for some of the contradictory results.
Future association studies on the link between CYP2D6 genotype and tamoxifen
treatment efficacy should account for combination therapy and CYP2D6 inhibition,
and interrogate as many CYP2D6 alleles as possible.

PMID: 22531359 [PubMed - as supplied by publisher]