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Erschienen in: Cancer Causes & Control 1/2019

12.12.2018 | Original paper

CYP2D6-inhibiting medication use and inherited CYP2D6 variation in relation to adverse breast cancer outcomes after tamoxifen therapy

verfasst von: Sophie E. Mayer, Noel S. Weiss, Jessica Chubak, David R. Doody, Christopher S. Carlson, Karen W. Makar, Michelle A. Wurscher, Kathleen E. Malone

Erschienen in: Cancer Causes & Control | Ausgabe 1/2019

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Abstract

Purpose

Tamoxifen is widely used to reduce the risk of breast cancer (BC) recurrence and extend disease-free survival among women with estrogen-sensitive breast cancers. Tamoxifen efficacy is thought to be attributable to its active metabolite, which is formed through a reaction catalyzed by the P450 enzyme, CYP2D6. Inhibition of tamoxifen metabolism as a result of germline genetic variation and/or use of CYP2D6-inhibiting medications (“inhibitors”) is hypothesized to increase the risk of adverse BC outcomes among women taking tamoxifen.

Methods

The present cohort study of 960 women diagnosed with early-stage BC between 1993 and 1999 examined the association between concomitant use of CYP2D6 inhibitors and adjuvant tamoxifen and the risk of adverse BC outcomes (recurrence, second primary BC, BC mortality), both overall and according to CYP2D6 metabolic phenotype.

Results

Six or more months of CYP2D6 inhibitor use concomitant with tamoxifen was not associated with any appreciable increase in risk of recurrence or second primary BC or BC mortality, and there was no clear evidence of variation by CYP2D6 metabolic phenotype.

Conclusions

These results are consistent with the relatively few other large, population-based studies conducted to date that have not observed an increased risk of adverse BC outcomes associated with CYP2D6 inhibition.
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Metadaten
Titel
CYP2D6-inhibiting medication use and inherited CYP2D6 variation in relation to adverse breast cancer outcomes after tamoxifen therapy
verfasst von
Sophie E. Mayer
Noel S. Weiss
Jessica Chubak
David R. Doody
Christopher S. Carlson
Karen W. Makar
Michelle A. Wurscher
Kathleen E. Malone
Publikationsdatum
12.12.2018
Verlag
Springer International Publishing
Erschienen in
Cancer Causes & Control / Ausgabe 1/2019
Print ISSN: 0957-5243
Elektronische ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-018-1117-x

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