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Prediction of tamoxifen outcome by genetic variation of CYP2D6 in post‐menopausal women with early breast cancer
Author(s) -
Brauch Hiltrud,
Schwab Matthias
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12229
Subject(s) - tamoxifen , breast cancer , pharmacogenetics , cyp2d6 , medicine , oncology , cancer , gynecology , oestrogen receptor , pharmacodynamics , bioinformatics , genotype , biology , pharmacokinetics , genetics , cytochrome p450 , metabolism , gene
The question of whether genetic polymorphisms of CYP2D6 can affect treatment outcome in patients with early post‐menopausal oestrogen receptor ( ER )‐positive breast cancer has been a matter of debate over the past few years. In this article we revisit the hypothesis of CYP2D6 being a potential tamoxifen outcome predictor and provide detailed insight into the ongoing controversy that prevented the CYP2D6 marker from being accepted by the scientific and clinical community. We summarize the available pharmacokinetic, pharmacodynamic and pharmacogenetic evidence and resolve the controversy based on the recognized methodological and statistical issues. The cumulative evidence suggests that genotyping for CYP2D6 is clinically relevant in post‐menopausal women. This is important, because the clarification of this issue has the potential to resolve a clinical management question that is relevant to hundreds of thousands of women diagnosed with ER ‐positive breast cancer each year, who should not be denied effective endocrine therapy.