Endoxifen levels and metabolic phenotype-associated factors in Mexican Mestizo patients under tamoxifen treatment

Pharmacogenomics. 2020 Aug;21(13):929-943. doi: 10.2217/pgs-2020-0061. Epub 2020 Aug 18.

Abstract

Aim: To evaluate plasma endoxifen levels and metabolic phenotype-associated factors in Mexican Mestizo patients under tamoxifen treatment. Patients & methods: A total of 138 breast cancer patients under tamoxifen treatment were cross-sectionally evaluated and side effects (SE) were recorded. CYP2D6 genetic phenotypes (GP) and metabolic phenotypes (MP) were assessed (metabolic poor [mPM], intermediate [mIM], normal [mNM], and ultrarapid [mUM] metabolizer). Associations were tested in uni-multivariate models for endoxifen >5.9 ng/ml and for mNM + mUM MP. Results: The main SE was hot flashes (62%). Distribution of the CYP2D6 MP was 4.3% mPM; 14.5% mIM; 75.4% mNM; and 5.8% mUM. Endoxifen >5.9 ng/ml was partially associated with SE (p = 0.06); the mNM + mUM MP was associated with treatment time (p = 0.03). Conclusion: The endoxifen-associated factors in Mexican Mestizo patients remain inconclusive, although treatment time was associated with MP.

Keywords: CYP2D6; Mexican Mestizos; breast cancer; endoxifen; metabolic phenotype; tamoxifen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / blood*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Cross-Sectional Studies
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP2D6 / metabolism
  • Female
  • Genotype
  • Humans
  • Mexico
  • Middle Aged
  • Phenotype
  • Racial Groups / genetics
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / blood
  • Tamoxifen / therapeutic use*

Substances

  • Tamoxifen
  • 4-hydroxy-N-desmethyltamoxifen
  • Cytochrome P-450 CYP2D6