CYP2D6 Genotype Predicts Tamoxifen Discontinuation and Prognosis in Patients With Breast Cancer

Wei He* (Corresponding Author), Felix Grassmann, Mikael Eriksson, Erik Eliasson, Sara Margolin, Linda Thorén, Per Hall, Kamila Czene

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

PURPOSE: To examine the association between CYP2D6 genotype, discontinuation of tamoxifen therapy, and prognosis for breast cancer.

PATIENTS AND METHODS: We conducted a prospective-retrospective study linking data from a clinical breast cancer register, the Swedish Prescribed Drug Register, and self-reported questionnaires. We genotyped CYP2D6 in 1,309 patients with breast cancer who were treated with tamoxifen and were diagnosed from 2005 to 2012; they were categorized as poor, intermediate, normal, or ultrarapid CYP2D6 metabolizers. We investigated whether metabolizer status was associated with tamoxifen discontinuation and prognosis for breast cancer using Cox regression analysis.

RESULTS: The 6-month discontinuation rates of tamoxifen among poor, intermediate, normal, and ultrarapid CYP2D6 metabolizers were 7.1%, 7.6%, 6.7%, and 18.8%, respectively. A U-shaped association was found between CYP2D6 metabolizer status and breast cancer-specific mortality, with adjusted hazard ratios of 2.59 (95% CI, 1.01 to 6.67) for poor, 1.48 (95% CI, 0.72 to 3.05) for intermediate, 1 (reference) for normal, and 4.52 (95% CI, 1.42 to 14.37) for ultrarapid CYP2D6 metabolizers.

CONCLUSION: Both poor and ultrarapid CYP2D6 metabolizers of tamoxifen have a worse prognosis for breast cancer compared with normal metabolizers after receiving a standard dose of tamoxifen. This U-shaped association might call for individualized tamoxifen dosage.

Original languageEnglish
Pages (from-to)548-557
Number of pages10
JournalJournal of Clinical Oncology
Volume38
Issue number6
Early online date4 Dec 2019
DOIs
Publication statusPublished - 20 Feb 2020

Keywords

  • ADJUVANT HORMONE-THERAPY
  • CLINICAL-OUTCOMES
  • CYTOCHROME-P450 2D6
  • ESTROGEN-RECEPTOR
  • GENETIC POLYMORPHISMS
  • HOT FLASHES
  • METABOLISM
  • PHARMACOGENETICS
  • RISK-FACTORS
  • WOMEN

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