Concomitant CYP2D6 inhibitor use and plasma metabolite levels in breast cancer patients treated with tamoxifen

P. Fox, B. Balakrishnar, A. Menzies, C. Liddle, S. Coulter, P. Provan, V. Gebski, R. Hui, R. Kefford, N. Wilcken, R. Balleine, H. Gurney

Research output: Contribution to journalMeeting abstractpeer-review


Background: The rate-limiting step in tamoxifen biotransformation to
endoxifen is cytochrome p450 2D6 (CYP2D6) activity. CYP2D6 inhibitors may result in decreased endoxifen levels, although are commonly used to treat depression and hot flushes. The aim of this study was to examine the association between CYP2D6 inhibitor use and tamoxifen metabolite levels in breast cancer patients.

Methods: Plasma endoxifen levels were measured using High Performance Liquid Chromatography/Mass Spectroscopy in 112 patients taking tamoxifen 20 mg daily. Patients co-prescribed CYP2D6 inhibitors were included in this analysis.

Results: 22 of 112 patients (20%) were co-prescribed tamoxifen and a
CYP2D6 inhibitor. These included 11 minimal, 9 weak-moderate and 2
strong inhibitors. Inhibitors were prescribed for depression/anxiety (n = 11), hot flushes (n = 7) and allergic disorders (n = 4). The mean endoxifen level in patients taking no inhibitor (n = 90), minimal, weak-moderate and strong inhibitors were 28.9, 21.3, 23.1 and 4.9 nM, respectively (p = 0.01). There was an association between the metabolic ratio of endoxifen compared with its precursor N-desmethyltamoxifen and inhibitor use (p = 0.03), consistent with an impact of inhibitors on CYP2D6 activity.

Conclusions: CYP2D6 inhibitor use was associated with lower plasma
endoxifen levels in patients taking endoxifen. The interaction between
CYP2D6 inhibitors and other factors that may affect endoxifen levels, in
particular CYP2D6 genotype, is an issue requiring further study.
Original languageEnglish
Pages (from-to)52-52
Number of pages1
JournalAsia-Pacific Journal of Clinical Oncology
Issue numberSupplement 2
Early online date31 Jul 2012
Publication statusPublished - 31 Jul 2012
Externally publishedYes


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