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Case Reports
. 2013 Dec;2(1):52.
doi: 10.1186/2193-1801-2-52. Epub 2013 Feb 15.

CYP2D6 Genotypes, Endoxifen Levels, and Disease Recurrence in 224 Filipino and Vietnamese Women Receiving Adjuvant Tamoxifen for Operable Breast Cancer

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Case Reports

CYP2D6 Genotypes, Endoxifen Levels, and Disease Recurrence in 224 Filipino and Vietnamese Women Receiving Adjuvant Tamoxifen for Operable Breast Cancer

Richard R Love et al. Springerplus. .
Free PMC article

Abstract

Background: While tamoxifen activity is mainly due to endoxifen and the concentration of this active metabolite is, in part, controlled by CYP2D6 metabolic status, clinical correlative studies have produced mixed results.

Findings: In an exploratory study, we determined the CYP2D6 metabolic status and plasma concentrations of endoxifen among 224 Filipino and Vietnamese women participating in a clinical trial of adjuvant hormonal therapy for operable breast cancer. We further conducted a nested-case-control study among 48 women (half with recurrent disease, half without) investigating the relationship of endoxifen concentrations and recurrence of disease. We found a significant association of reduced endoxifen plasma concentrations with functionally important CYP2D6 genotypes. High endoxifen concentrations were associated with higher risk of recurrence; with a quadratic trend fitted to a stratified Cox proportional hazards regression model, the likelihood ratio p-value was 0.002. The trend also showed that in 8 out of 9 pairs with low endoxifen concentrations, the recurrent case had lower endoxifen levels than the matched control.

Conclusions: This exploratory analysis suggests that there is an optimal range for endoxifen concentrations to achieve favorable effects as adjuvant therapy. In particular, at higher concentrations (>70 ng.ml), endoxifen may promote recurrence.

Figures

Figure 1
Figure 1
Endoxifen plasma concentrations by CYP2D6 genotype metabolic status in Filipino (n = 138) and Vietnamese (n = 86) patients (p = 0.0001 for trend: normal > intermediate > slow).
Figure 2
Figure 2
Plot of the absolute difference in endoxifen levels between members of each matched pair by the endoxifen level of the recurrence member of the matched pair.

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