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CYP2D6 Genotype and Tamoxifen Response for Breast Cancer: A Systematic Review and Meta-Analysis

Lum, DW; Perel, P; Hingorani, AD; Holmes, MV; (2013) CYP2D6 Genotype and Tamoxifen Response for Breast Cancer: A Systematic Review and Meta-Analysis. PLoS One , 8 (10) , Article e76648. 10.1371/journal.pone.0076648. Green open access

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Abstract

Objective To evaluate evidence on the association between CYP2D6 genotype and tamoxifen response through. Design Systematic review and meta-analysis of prospective, cross-sectional and case-control studies published to 2012. For each study, relative risks and 95% confidence intervals were extracted and pooled with a fixed and random effects model. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. Data Sources PubMed (inception-2012) and EMBASE (inception-2012). Eligibility Criteria for Selecting Studies Criteria for inclusion were studies reporting breast cancer outcomes in patients treated with tamoxifen and genotyped for polymorphisms in the CYP2D6 gene. Results Twenty-five studies of 13,629 individuals were identified, of which 22 investigated the association of CYP2D6 genotype with outcomes in breast cancer women all receiving tamoxifen treatment (“treatment-only” design). Three randomized trials evaluated the effect of CYP2D6 genotype on tamoxifen response (“effect modification” design). In analysis of treatment-only studies, the relative risk (RR) of all-cause mortality (>307 events in 4,936 patients) for carriers of a CYP2D6 reduced function allele was 1.11 (95% confidence interval (CI): 0.94 to 1.31) compared to individuals with normal/increased function CYP2D6 alleles. When we investigated a composite outcome including all-cause mortality and surrogate endpoints for overall survival (>307 events in 6,721 patients), carriers of a CYP2D6 reduced function allele had a RR of 1.27 (95% CI: 1.11 to 1.45). From two randomized trials that permitted effect-modification analysis, one had only 154 patients and showed evidence of effect modification of tamoxifen by CYP2D6 genotype for distant recurrence but was directionally opposite to that predicted, whereas a larger trial of 2,537 patients failed to show evidence of effect modification for breast cancer-free interval (P values for interaction 0.02 and 0.44, respectively). Conclusions Based on these findings, there is insufficient evidence to recommend CYP2D6 genotyping to guide tamoxifen treatment.

Type: Article
Title: CYP2D6 Genotype and Tamoxifen Response for Breast Cancer: A Systematic Review and Meta-Analysis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0076648
Publisher version: http://dx.doi.org/10.1371/journal.pone.0076648
Language: English
Additional information: © 2013 Lum et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3788742
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
URI: http://discovery.ucl.ac.uk/id/eprint/1417114
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