Skip to main content
padlock icon - secure page this page is secure

Comprehensive assessment of cytochromes P450 and transporter genetics with endoxifen concentration during tamoxifen treatment

Buy Article:

$52.00 + tax (Refund Policy)

Objectives

Tamoxifen bioactivation to endoxifen is mediated primarily by CYP2D6; however, considerable variability remains unexplained. Our aim was to perform a comprehensive assessment of the effect of genetic variation in tamoxifen-relevant enzymes and transporters on steady-state endoxifen concentrations.

Patients and methods

Comprehensive genotyping of CYP enzymes and transporters was performed using the iPLEX ADME PGx Pro Panel in 302 tamoxifen-treated breast cancer patients. Predicted activity phenotype for 19 enzymes and transporters were analyzed for univariate association with endoxifen concentration, and then adjusted for CYP2D6 and clinical covariates.

Results

In univariate analysis, higher activity of CYP2C8 (regression β=0.22, P=0.020) and CYP2C9 (β=0.20, P=0.04), lower body weight (β=−0.014, P<0.0001), and endoxifen measurement during winter (each β<−0.39, P=0.002) were associated with higher endoxifen concentrations. After adjustment for the CYP2D6 diplotype, weight, and season, CYP2C9 remained significantly associated with higher concentrations (P=0.02), but only increased the overall model R 2 by 1.3%.

Conclusion

Our results further support a minor contribution of CYP2C9 genetic variability toward steady-state endoxifen concentrations. Integration of clinician and genetic variables into individualized tamoxifen dosing algorithms would marginally improve their accuracy and potentially enhance tamoxifen treatment outcomes.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
No Metrics

Keywords: CYP2C9; CYP2D6; endoxifen; pharmacogenomics; season; tamoxifen

Document Type: Research Article

Affiliations: 1: Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan 2: UNC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 3: DeBartolo Family Personalized Medicine Institute, Moffitt Cancer Center, Tampa, Florida 4: Department of Clinical Pharmacology, Indiana University, Indianapolis, Indiana 5: UNC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, Bon Secours Cancer Institute, Richmond, Virginia, USA

Publication date: November 1, 2017

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more