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

Abstract 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 P...

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Autores principales:	Andrea DeCensi, Harriet Johansson, Thomas Helland, Matteo Puntoni, Debora Macis, Valentina Aristarco, Silvia Caviglia, Tania Buttiron Webber, Irene Maria Briata, Mauro D’Amico, Davide Serrano, Aliana Guerrieri-Gonzaga, Ersilia Bifulco, Steinar Hustad, Håvard Søiland, Luca Boni, Bernardo Bonanni, Gunnar Mellgren
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/970405befd6e48368a4c4d7033f964aa
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spelling	oai:doaj.org-article:970405befd6e48368a4c4d7033f964aa2021-12-02T11:44:49ZAssociation of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial10.1038/s41523-021-00236-62374-4677https://doaj.org/article/970405befd6e48368a4c4d7033f964aa2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00236-6https://doaj.org/toc/2374-4677Abstract 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 .Andrea DeCensiHarriet JohanssonThomas HellandMatteo PuntoniDebora MacisValentina AristarcoSilvia CavigliaTania Buttiron WebberIrene Maria BriataMauro D’AmicoDavide SerranoAliana Guerrieri-GonzagaErsilia BifulcoSteinar HustadHåvard SøilandLuca BoniBernardo BonanniGunnar MellgrenNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-5 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Andrea DeCensi Harriet Johansson Thomas Helland Matteo Puntoni Debora Macis Valentina Aristarco Silvia Caviglia Tania Buttiron Webber Irene Maria Briata Mauro D’Amico Davide Serrano Aliana Guerrieri-Gonzaga Ersilia Bifulco Steinar Hustad Håvard Søiland Luca Boni Bernardo Bonanni Gunnar Mellgren Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial
description	Abstract 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	article
author	Andrea DeCensi Harriet Johansson Thomas Helland Matteo Puntoni Debora Macis Valentina Aristarco Silvia Caviglia Tania Buttiron Webber Irene Maria Briata Mauro D’Amico Davide Serrano Aliana Guerrieri-Gonzaga Ersilia Bifulco Steinar Hustad Håvard Søiland Luca Boni Bernardo Bonanni Gunnar Mellgren
author_facet	Andrea DeCensi Harriet Johansson Thomas Helland Matteo Puntoni Debora Macis Valentina Aristarco Silvia Caviglia Tania Buttiron Webber Irene Maria Briata Mauro D’Amico Davide Serrano Aliana Guerrieri-Gonzaga Ersilia Bifulco Steinar Hustad Håvard Søiland Luca Boni Bernardo Bonanni Gunnar Mellgren
author_sort	Andrea DeCensi
title	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_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_sort	association of cyp2d6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/970405befd6e48368a4c4d7033f964aa
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Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial

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