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(Z)-Endoxifen and Early Recurrence of Breast Cancer: An Explorative Analysis in a Prospective Brazilian Study

Adherence to treatment and use of co-medication, but also molecular factors such as CYP2D6 genotype, affect tamoxifen metabolism, with consequences for early breast cancer prognosis. In a prospective study of 149 tamoxifen-treated early-stage breast cancer patients from Brazil followed up for 5 year...

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Autores principales: Almeida, Thais, Schroth, Werner, Nardin, Jeanine, Mürdter, Thomas E., Winter, Stefan, Picolotto, Solane, Hoppe, Reiner, Kogin, Jenifer, Gaio, Elisa, Dasenbrock, Angela, Skrsypcsak, Raquel Cristina, de Noronha, Lucia, Schwab, Matthias, Brauch, Hiltrud, Casali-da-Rocha, José Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030524/
https://www.ncbi.nlm.nih.gov/pubmed/35455627
http://dx.doi.org/10.3390/jpm12040511
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author Almeida, Thais
Schroth, Werner
Nardin, Jeanine
Mürdter, Thomas E.
Winter, Stefan
Picolotto, Solane
Hoppe, Reiner
Kogin, Jenifer
Gaio, Elisa
Dasenbrock, Angela
Skrsypcsak, Raquel Cristina
de Noronha, Lucia
Schwab, Matthias
Brauch, Hiltrud
Casali-da-Rocha, José Claudio
author_facet Almeida, Thais
Schroth, Werner
Nardin, Jeanine
Mürdter, Thomas E.
Winter, Stefan
Picolotto, Solane
Hoppe, Reiner
Kogin, Jenifer
Gaio, Elisa
Dasenbrock, Angela
Skrsypcsak, Raquel Cristina
de Noronha, Lucia
Schwab, Matthias
Brauch, Hiltrud
Casali-da-Rocha, José Claudio
author_sort Almeida, Thais
collection PubMed
description Adherence to treatment and use of co-medication, but also molecular factors such as CYP2D6 genotype, affect tamoxifen metabolism, with consequences for early breast cancer prognosis. In a prospective study of 149 tamoxifen-treated early-stage breast cancer patients from Brazil followed up for 5 years, we investigated the association between the active tamoxifen metabolite (Z)-endoxifen at 3 months and event-free survival (EFS) adjusted for clinico-pathological factors. Twenty-five patients (16.8%) had recurred or died at a median follow-up of 52.3 months. When we applied a putative 15 nM threshold used in previous independent studies, (Z)-endoxifen levels below the threshold showed an association with shorter EFS in univariate analysis (p = 0.045) and after adjustment for stage (HR 2.52; 95% CI 1.13–5.65; p = 0.024). However, modeling of plasma concentrations with splines instead of dichotomization did not verify a significant association with EFS (univariate analysis: p = 0.158; adjusted for stage: p = 0.117). Hence, in our small exploratory study, the link between impaired tamoxifen metabolism and early breast cancer recurrence could not be unanimously demonstrated. This inconsistency justifies larger modeling studies backed up by mechanistic pharmacodynamic analyses to shed new light on this suspected association and the stipulation of an appropriate predictive (Z)-endoxifen threshold.
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spelling pubmed-90305242022-04-23 (Z)-Endoxifen and Early Recurrence of Breast Cancer: An Explorative Analysis in a Prospective Brazilian Study Almeida, Thais Schroth, Werner Nardin, Jeanine Mürdter, Thomas E. Winter, Stefan Picolotto, Solane Hoppe, Reiner Kogin, Jenifer Gaio, Elisa Dasenbrock, Angela Skrsypcsak, Raquel Cristina de Noronha, Lucia Schwab, Matthias Brauch, Hiltrud Casali-da-Rocha, José Claudio J Pers Med Article Adherence to treatment and use of co-medication, but also molecular factors such as CYP2D6 genotype, affect tamoxifen metabolism, with consequences for early breast cancer prognosis. In a prospective study of 149 tamoxifen-treated early-stage breast cancer patients from Brazil followed up for 5 years, we investigated the association between the active tamoxifen metabolite (Z)-endoxifen at 3 months and event-free survival (EFS) adjusted for clinico-pathological factors. Twenty-five patients (16.8%) had recurred or died at a median follow-up of 52.3 months. When we applied a putative 15 nM threshold used in previous independent studies, (Z)-endoxifen levels below the threshold showed an association with shorter EFS in univariate analysis (p = 0.045) and after adjustment for stage (HR 2.52; 95% CI 1.13–5.65; p = 0.024). However, modeling of plasma concentrations with splines instead of dichotomization did not verify a significant association with EFS (univariate analysis: p = 0.158; adjusted for stage: p = 0.117). Hence, in our small exploratory study, the link between impaired tamoxifen metabolism and early breast cancer recurrence could not be unanimously demonstrated. This inconsistency justifies larger modeling studies backed up by mechanistic pharmacodynamic analyses to shed new light on this suspected association and the stipulation of an appropriate predictive (Z)-endoxifen threshold. MDPI 2022-03-22 /pmc/articles/PMC9030524/ /pubmed/35455627 http://dx.doi.org/10.3390/jpm12040511 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Almeida, Thais
Schroth, Werner
Nardin, Jeanine
Mürdter, Thomas E.
Winter, Stefan
Picolotto, Solane
Hoppe, Reiner
Kogin, Jenifer
Gaio, Elisa
Dasenbrock, Angela
Skrsypcsak, Raquel Cristina
de Noronha, Lucia
Schwab, Matthias
Brauch, Hiltrud
Casali-da-Rocha, José Claudio
(Z)-Endoxifen and Early Recurrence of Breast Cancer: An Explorative Analysis in a Prospective Brazilian Study
title (Z)-Endoxifen and Early Recurrence of Breast Cancer: An Explorative Analysis in a Prospective Brazilian Study
title_full (Z)-Endoxifen and Early Recurrence of Breast Cancer: An Explorative Analysis in a Prospective Brazilian Study
title_fullStr (Z)-Endoxifen and Early Recurrence of Breast Cancer: An Explorative Analysis in a Prospective Brazilian Study
title_full_unstemmed (Z)-Endoxifen and Early Recurrence of Breast Cancer: An Explorative Analysis in a Prospective Brazilian Study
title_short (Z)-Endoxifen and Early Recurrence of Breast Cancer: An Explorative Analysis in a Prospective Brazilian Study
title_sort (z)-endoxifen and early recurrence of breast cancer: an explorative analysis in a prospective brazilian study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030524/
https://www.ncbi.nlm.nih.gov/pubmed/35455627
http://dx.doi.org/10.3390/jpm12040511
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