Cargando…

Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial

Low-dose tamoxifen halves recurrence in non-invasive breast cancer without significant adverse events. Some adjuvant trials with tamoxifen 20 mg/day had shown an association between low endoxifen levels (9–16 nM) and recurrence, but no association with CYP2D6 was shown in the NSABP P1 and P2 prevent...

Descripción completa

Detalles Bibliográficos
Autores principales: DeCensi, Andrea, Johansson, Harriet, Helland, Thomas, Puntoni, Matteo, Macis, Debora, Aristarco, Valentina, Caviglia, Silvia, Webber, Tania Buttiron, Briata, Irene Maria, D’Amico, Mauro, Serrano, Davide, Guerrieri-Gonzaga, Aliana, Bifulco, Ersilia, Hustad, Steinar, Søiland, Håvard, Boni, Luca, Bonanni, Bernardo, Mellgren, Gunnar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994552/
https://www.ncbi.nlm.nih.gov/pubmed/33767162
http://dx.doi.org/10.1038/s41523-021-00236-6
_version_ 1783669774790688768
author DeCensi, Andrea
Johansson, Harriet
Helland, Thomas
Puntoni, Matteo
Macis, Debora
Aristarco, Valentina
Caviglia, Silvia
Webber, Tania Buttiron
Briata, Irene Maria
D’Amico, Mauro
Serrano, Davide
Guerrieri-Gonzaga, Aliana
Bifulco, Ersilia
Hustad, Steinar
Søiland, Håvard
Boni, Luca
Bonanni, Bernardo
Mellgren, Gunnar
author_facet DeCensi, Andrea
Johansson, Harriet
Helland, Thomas
Puntoni, Matteo
Macis, Debora
Aristarco, Valentina
Caviglia, Silvia
Webber, Tania Buttiron
Briata, Irene Maria
D’Amico, Mauro
Serrano, Davide
Guerrieri-Gonzaga, Aliana
Bifulco, Ersilia
Hustad, Steinar
Søiland, Håvard
Boni, Luca
Bonanni, Bernardo
Mellgren, Gunnar
author_sort DeCensi, Andrea
collection PubMed
description Low-dose tamoxifen halves recurrence in non-invasive breast cancer without significant adverse events. Some adjuvant trials with tamoxifen 20 mg/day had shown an association between low endoxifen levels (9–16 nM) and recurrence, but no association with CYP2D6 was shown in the NSABP P1 and P2 prevention trials. We studied the association of CYP2D6 genotype and tamoxifen metabolites with tumor biomarkers and recurrence in a randomized phase III trial of low-dose tamoxifen. Median (IQR) endoxifen levels at year 1 were 8.4 (5.3–11.4) in patients who recurred vs 7.5 (5.1–10.2) in those who did not recur (p = 0.60). Tamoxifen and metabolites significantly decreased C-reactive protein (CRP, p < 0.05), and a CRP increase after 3 years was associated with higher risk of recurrence (HR = 4.37, 95% CI, 1.14–16.73, P = 0.03). In conclusion, endoxifen is below 9 nM in most subjects treated with 5 mg/day despite strong efficacy and there is no association with recurrence, suggesting that the reason for tamoxifen failure is not poor drug metabolism. Trial registration: ClinicalTrials.gov, Identifier: NCT01357772.
format Online
Article
Text
id pubmed-7994552
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-79945522021-04-16 Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial DeCensi, Andrea Johansson, Harriet Helland, Thomas Puntoni, Matteo Macis, Debora Aristarco, Valentina Caviglia, Silvia Webber, Tania Buttiron Briata, Irene Maria D’Amico, Mauro Serrano, Davide Guerrieri-Gonzaga, Aliana Bifulco, Ersilia Hustad, Steinar Søiland, Håvard Boni, Luca Bonanni, Bernardo Mellgren, Gunnar NPJ Breast Cancer Brief Communication Low-dose tamoxifen halves recurrence in non-invasive breast cancer without significant adverse events. Some adjuvant trials with tamoxifen 20 mg/day had shown an association between low endoxifen levels (9–16 nM) and recurrence, but no association with CYP2D6 was shown in the NSABP P1 and P2 prevention trials. We studied the association of CYP2D6 genotype and tamoxifen metabolites with tumor biomarkers and recurrence in a randomized phase III trial of low-dose tamoxifen. Median (IQR) endoxifen levels at year 1 were 8.4 (5.3–11.4) in patients who recurred vs 7.5 (5.1–10.2) in those who did not recur (p = 0.60). Tamoxifen and metabolites significantly decreased C-reactive protein (CRP, p < 0.05), and a CRP increase after 3 years was associated with higher risk of recurrence (HR = 4.37, 95% CI, 1.14–16.73, P = 0.03). In conclusion, endoxifen is below 9 nM in most subjects treated with 5 mg/day despite strong efficacy and there is no association with recurrence, suggesting that the reason for tamoxifen failure is not poor drug metabolism. Trial registration: ClinicalTrials.gov, Identifier: NCT01357772. Nature Publishing Group UK 2021-03-25 /pmc/articles/PMC7994552/ /pubmed/33767162 http://dx.doi.org/10.1038/s41523-021-00236-6 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Brief Communication
DeCensi, Andrea
Johansson, Harriet
Helland, Thomas
Puntoni, Matteo
Macis, Debora
Aristarco, Valentina
Caviglia, Silvia
Webber, Tania Buttiron
Briata, Irene Maria
D’Amico, Mauro
Serrano, Davide
Guerrieri-Gonzaga, Aliana
Bifulco, Ersilia
Hustad, Steinar
Søiland, Håvard
Boni, Luca
Bonanni, Bernardo
Mellgren, Gunnar
Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial
title Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial
title_full Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial
title_fullStr Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial
title_full_unstemmed Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial
title_short Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial
title_sort association of cyp2d6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994552/
https://www.ncbi.nlm.nih.gov/pubmed/33767162
http://dx.doi.org/10.1038/s41523-021-00236-6
work_keys_str_mv AT decensiandrea associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT johanssonharriet associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT hellandthomas associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT puntonimatteo associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT macisdebora associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT aristarcovalentina associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT cavigliasilvia associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT webbertaniabuttiron associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT briatairenemaria associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT damicomauro associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT serranodavide associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT guerrierigonzagaaliana associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT bifulcoersilia associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT hustadsteinar associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT søilandhavard associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT boniluca associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT bonannibernardo associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial
AT mellgrengunnar associationofcyp2d6genotypeandtamoxifenmetaboliteswithbreastcancerrecurrenceinalowdosetrial