The impact of CYP2D6-predicted phenotype on tamoxifen treatment outcome in patients with metastatic breast cancer.

Abstract:

BACKGROUND:Cytochrome P450 2D6 (CYP2D6) has a crucial role in the metabolic conversion of tamoxifen into the active metabolite endoxifen. In this cohort study, the effect of CYP2D6-predicted phenotype, defined as the combined effect of CYP2D6 genetic variation and concomitant use of CYP2D6-inhibiting medication, on time to breast cancer progression (TTP) and overall survival (OS) in women who use tamoxifen for metastatic breast cancer (MBC) was examined. METHODS:We selected patients treated with tamoxifen (40 mg per day) for hormone receptor-positive MBC from whom a blood sample for pharmacogenetic analysis (CYP2D6*3, *4, *5, *6, *10 and *41) was available. Patient charts (n=102) were reviewed to assess TTP and OS, and to determine whether CYP2D6 inhibitors were prescribed during tamoxifen treatment. RESULTS:OS was significantly shorter in patients with a poor CYP2D6 metaboliser phenotype, compared with extensive metabolisers (HR=2.09; P=0.034; 95% CI: 1.06-4.12). Co-administration of CYP2D6 inhibitors alone was also associated with a worse OS (HR=3.55; P=0.002; 95% CI: 1.59-7.96) and TTP (HR=2.97; P=0.008; 95% CI: 1.33-6.67) compared with patients without CYP2D6 inhibitors. CONCLUSION:CYP2D6 phenotype is an important predictor of treatment outcome in women who are receiving tamoxifen for MBC. Co-administration of CYP2D6 inhibitors worsens treatment outcome of tamoxifen and should therefore be handled with care.

journal_name

Br J Cancer

authors

Lammers LA,Mathijssen RH,van Gelder T,Bijl MJ,de Graan AJ,Seynaeve C,van Fessem MA,Berns EM,Vulto AG,van Schaik RH

doi

10.1038/sj.bjc.6605800

subject

Has Abstract

pub_date

2010-09-07 00:00:00

pages

765-71

issue

6

eissn

0007-0920

issn

1532-1827

pii

6605800

journal_volume

103

pub_type

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