Cytochrome P450 2D6 activity predicts discontinuation of tamoxifen therapy in breast cancer patients

J. M. Rae, M. J. Sikora, N. L. Henry, L. Li, S. Kim, S. Oesterreich, T. C. Skaar, A. T. Nguyen, Z. Desta, A. M. Storniolo, D. A. Flockhart, D. F. Hayes, V. Stearns

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68 Scopus citations

Abstract

The selective estrogen receptor modulator tamoxifen is routinely used for treatment and prevention of estrogen-receptor-positive breast cancer. Studies of tamoxifen adherence suggest that over half of patients discontinue treatment before the recommended 5 years. We hypothesized that polymorphisms in CYP2D6, the enzyme responsible for tamoxifen activation, predict for tamoxifen discontinuation. Tamoxifen-treated women (n=297) were genotyped for CYP2D6 variants and assigned a 'score' based on predicted allele activities from 0 (no activity) to 2 (high activity). Correlation between CYP2D6 score and discontinuation rates at 4 months was tested. We observed a strong nonlinear correlation between higher CYP2D6 score and increased rates of discontinuation (r2 = 0.935, P = 0.018). These data suggest that presence of active CYP2D6 alleles may predict for higher likelihood of tamoxifen discontinuation. Therefore, patients who may be most likely to benefit from tamoxifen may paradoxically be most likely to discontinue treatment prematurely.

Original languageEnglish (US)
Pages (from-to)258-264
Number of pages7
JournalPharmacogenomics Journal
Volume9
Issue number4
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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    Rae, J. M., Sikora, M. J., Henry, N. L., Li, L., Kim, S., Oesterreich, S., Skaar, T. C., Nguyen, A. T., Desta, Z., Storniolo, A. M., Flockhart, D. A., Hayes, D. F., & Stearns, V. (2009). Cytochrome P450 2D6 activity predicts discontinuation of tamoxifen therapy in breast cancer patients. Pharmacogenomics Journal, 9(4), 258-264. https://doi.org/10.1038/tpj.2009.14