Association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort

Breast Cancer Res Treat. 2009 Oct;117(3):571-5. doi: 10.1007/s10549-009-0309-1. Epub 2009 Jan 20.


Women with reduced CYP2D6 activity have low endoxifen concentrations and likely worse long term benefits from tamoxifen. We investigated the association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. We collected hot flash frequency and severity data over 12 months from 297 women initiating tamoxifen. We performed CYP2D6 genotyping using the AmpliChip CYP450 test and correlated inherited genetic polymorphisms in CYP2D6 and tamoxifen-induced hot flashes. Intermediate metabolizers had greater mean hot flash scores after 4 months of tamoxifen therapy (44.3) compared to poor metabolizers (20.6, P = 0.038) or extensive metabolizers (26.9, P = 0.011). At 4 months, we observed a trend toward fewer severe hot flashes in poor metabolizers compared to intermediate plus extensive metabolizers (P = 0.062). CYP2D6 activity may be a modest predictive factor for tamoxifen-induced hot flashes. The presence or absence of hot flashes should not be used to determine tamoxifen's efficacy.

Trial registration: NCT00228930.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / prevention & control
  • Cohort Studies
  • Cytochrome P-450 CYP2D6 / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Hot Flashes / chemically induced
  • Hot Flashes / genetics*
  • Humans
  • Polymorphism, Genetic
  • Selective Estrogen Receptor Modulators / adverse effects*
  • Tamoxifen / adverse effects*


  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • Cytochrome P-450 CYP2D6

Associated data