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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number34
Journalnpj Breast Cancer
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 2021

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

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