title: Influence of CYP2D6 polymorphisms on serum levels of tamoxifen metabolites in Spanish women with breast cancer.
abstract: BACKGROUND
  Estrogen receptor-positive breast cancer tumors depend on estrogen signaling for their growth and replication and can be treated by anti-estrogen therapy with tamoxifen. Polymorphisms of the CYP2D6 and CYP2C19 genes are associated with an impaired response to tamoxifen. The study objective was to investigate the impact of genetic polymorphisms in CYP2D6 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Spanish women with estrogen receptor-positive breast cancer who were candidates for tamoxifen therapy.
  
  
  METHODS
  We studied 90 women with estrogen receptor-positive breast cancer, using the AmpliChip CYP450 test to determine CYP2D6 and CYP2C19 gene variants. Plasma levels of tamoxifen and its metabolites were quantified by high-performance liquid chromatography.
  
  
  RESULTS
  The CYP2D6 phenotype was extensive metabolizer in 80%, intermediate metabolizer in 12.2%, ultra-rapid metabolizer in 2.2%, and poor metabolizer in 5.6% of patients, and the allele frequency was 35.0% for allele (*)1, 21.0% for *2, and 18.9% for *4. All poor metabolizers in this series were *4/*4, and their endoxifen and 4-hydroxy tamoxifen levels were 25% lower than those of extensive metabolizers. CYP2C19*2 allele, which has been related to breast cancer outcomes, was detected in 15.6% of the studied alleles.
  
  
  CONCLUSIONS
  CYP2D6*4/*4 genotype was inversely associated with 4-hydroxy tamoxifen and endoxifen levels. According to these results, CYP2D6 and CYP2C19 genotyping appears advisable before the prescription of tamoxifen therapy.
authors.affiliation: Clinical Biochemistry Services, San Cecilio University Hospital. Avd/ Doctor Olóriz s/n 18012, Granada, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Zafra-Ceres
authors.forename: Tomas
authors.initials: T
authors.lastname: de Haro
authors.forename: Esther
authors.initials: E
authors.lastname: Farez-Vidal
authors.forename: Isabel
authors.initials: I
authors.lastname: Blancas
authors.forename: Fernando
authors.initials: F
authors.lastname: Bandres
authors.forename: Eduardo Martinez
authors.initials: EM
authors.lastname: de Dueñas
authors.forename: Enrique
authors.initials: E
authors.lastname: Ochoa-Aranda
authors.forename: Jose A
authors.initials: JA
authors.lastname: Gomez-Capilla
authors.forename: Carolina
authors.initials: C
authors.lastname: Gomez-Llorente
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D006801:Humans; D011110:Polymorphism, Genetic; D013030:Spain; D013629:Tamoxifen / Q000097:blood*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6
keywords: CYP2C19; CYP2D6; endoxifen; estrogen-positive breast cancer; genetic diagnosis; tamoxifen