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01-01-2011 | Brief Report

Comprehensive CYP2D6 genotype and adherence affect outcome in breast cancer patients treated with tamoxifen monotherapy

Authors: Alastair M. Thompson, Andrea Johnson, Philip Quinlan, Grantland Hillman, Marcel Fontecha, Susan E. Bray, Colin A. Purdie, Lee B. Jordan, Roberta Ferraldeschi, Ayshe Latif, Kirsten D. Hadfield, Robert B. Clarke, Linda Ashcroft, D. Gareth Evans, Anthony Howell, Michele Nikoloff, Jeffrey Lawrence, William G. Newman

Published in: Breast Cancer Research and Treatment | Issue 1/2011

Abstract

The association between CYP2D6 genotype and outcome in breast cancer patients treated with adjuvant tamoxifen remains controversial. We assessed the influence of comprehensive versus limited CYP2D6 genotype in the context of tamoxifen adherence and co-medication in a large cohort of 618 patients. Genotyping of 33 CYP2D6 alleles used two archival cohorts from tamoxifen-treated women with invasive breast cancer (Dundee, n = 391; Manchester, n = 227). Estimates for recurrence-free survival (RFS) were calculated based on inferred CYP2D6 phenotypes using Kaplan–Meier and Cox proportional hazard models, adjusted for nodal status and tumour size. Patients with at least one reduced function CYP2D6 allele (60%) or no functional alleles (6%) had a non-significant trend for worse RFS: hazard ratio (HR) 1.52 (CI 0.98–2.36, P = 0.06). For post-menopausal women on tamoxifen monotherapy, the HR for recurrence in patients with reduced functional alleles was 1.96 (CI 1.05–3.66, P = 0.036). However, RFS analysis limited to four common CYP2D6 allelic variants was no longer significant (P = 0.39). The effect of CYP2D6 genotype was increased by adjusting for adherence to tamoxifen therapy, but not significantly changed when adjusted for co-administration of potent inhibitors of CYP2D6. Comprehensive genotyping of CYP2D6 and adherence to tamoxifen therapy may be useful to identify breast cancer patients most likely to benefit from adjuvant tamoxifen.

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Title: Comprehensive CYP2D6 genotype and adherence affect outcome in breast cancer patients treated with tamoxifen monotherapy
Authors: Alastair M. Thompson
Andrea Johnson
Philip Quinlan
Grantland Hillman
Marcel Fontecha
Susan E. Bray
Colin A. Purdie
Lee B. Jordan
Roberta Ferraldeschi
Ayshe Latif
Kirsten D. Hadfield
Robert B. Clarke
Linda Ashcroft
D. Gareth Evans
Anthony Howell
Michele Nikoloff
Jeffrey Lawrence
William G. Newman
Publication date: 01-01-2011
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2011
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-010-1139-x

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