The Influences of Adherence to Tamoxifen and CYP2D6 Pharmacogenetics on Plasma Concentrations of the Active Metabolite (Z)‐Endoxifen in Breast Cancer

The Influences of Adherence to Tamoxifen and CYP2D6 Pharmacogenetics on Plasma Concentrations of the Active Metabolite (Z)‐Endoxifen in Breast Cancer

Tamoxifen efficacy in breast cancer is suspected to depend on adherence and intact drug metabolism. We evaluated the role of adherence behavior and pharmacogenetics on the formation rate of (Z)‐endoxifen. In 192 Brazilian patients, we assessed plasma levels of tamoxifen and its metabolites at 3, 6,...

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Published in:Clinical and translational science Vol. 13; no. 2; pp. 284 - 292
Main Authors: Nardin, Jeanine Marie, Schroth, Werner, Almeida, Thais Abreu, Mürdter, Thomas, Picolotto, Solane, Vendramini, Evelyn Castillo Lima, Hoppe, Reiner, Kogin, Jenifer Primon, Miqueleto, Diandra, Moraes, Silvia Dark Robaskievicz, Schwab, Matthias, Pecoits‐Filho, Roberto Flavio, Brauch, Hiltrud, Casali‐da‐Rocha, José Claudio
Format: Journal Article
Language:English
Published: United States John Wiley & Sons, Inc 01-03-2020
John Wiley and Sons Inc
Wiley
Subjects:
Breast cancer
CYP2D6 protein
Cytochrome
Cytochrome P450
Drug metabolism
Drug stores
Enzymes
Mass spectroscopy
Metabolism
Metabolites
Patients
Pharmacogenetics
Plasma levels
Polymerase chain reaction
Questionnaires
Studies
Tamoxifen
Womens health
Brazil
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Summary:Tamoxifen efficacy in breast cancer is suspected to depend on adherence and intact drug metabolism. We evaluated the role of adherence behavior and pharmacogenetics on the formation rate of (Z)‐endoxifen. In 192 Brazilian patients, we assessed plasma levels of tamoxifen and its metabolites at 3, 6, and 12 months of treatment (liquid‐chromatography tandem mass spectrometry), adherence behavior (Morisky, Green, and Levine medication adherence scale), and cytochrome P450 2D6 (CYP2D6) and other pharmacogene polymorphisms (matrix‐assisted laser‐desorption‐ionization time of flight) mass spectrometry, real‐time polymerase chain reaction). Adherence explained 47% of the variability of tamoxifen plasma concentrations (P < 0.001). Although CYP2D6 alone explained 26.4%, the combination with adherence explained 40% of (Z)‐endoxifen variability at 12 months (P < 0.001). The influence of low adherence to not achieving relevant (Z)‐endoxifen levels was highest in patients with noncompromised CYP2D6 function (relative risk 3.65; 95% confidence interval 1.48–8.99). As a proof‐of‐concept, we demonstrated that (Z)‐endoxifen levels are influenced both by patient adherence to tamoxifen and CYP2D6, which is particularly relevant for patients with full CYP2D6 function.
Bibliography:These authors contributed equally to this work.
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ISSN:1752-8054
1752-8062
DOI:10.1111/cts.12707