title: CYP2D6 phenotype indicative for optimized antiestrogen efficacy associates with outcome in early breast cancer patients.
abstract: BACKGROUND
  Endoxifen serum concentrations seem to correlate with outcome in breast cancer (BC) patients. Concurrently, cytochrome P450 2D6 (CYP2D6) enzyme activity and dextromethorphan (DM) metabolism are deemed a surrogate marker for the formation of endoxifen. Here, we conducted a matched cohort study to determine the impact of an extensive CYP2D6 phenotype on relapse in patients with early-stage estrogen receptor (ER)-positive BC and adjuvant tamoxifen intake.
  
  
  METHODS
  CYP2D6 extensive metabolism was determined upon appropriate dextromethorphan/dextrorphan (DM/DX) urinary excretion ratios (≤0.30). Fifty-nine BC patients were identified as extensive phenotype metabolizers, while for 148 matched controls, CYP2D6 was not determined. Patients and controls did not differ with respect to age, stage, hormone receptor status, HER2, grade, menopausal status, chemotherapy and antihormonal therapy. Survival analysis was performed according to clinical follow-up.
  
  
  RESULTS
  Disease-free survival (DFS) of patients identified as extensive CYP2D6 metabolizers did not differ significantly from controls (p = 0.10). However, when patients with ER expression of ≤ 20 % were excluded from the analysis, DFS was associated with a more favorable outcome (p = 0.06).
  
  
  CONCLUSIONS
  This study suggests a positive association between extensive CYP2D6 metabolism and outcome in early-stage ER-positive BC patients using tamoxifen and in particular, when a sufficient number ERs are represented on the primary tumor.
authors.affiliation: OnkoZentrum, Klinik im Park, Zurich, Switzerland. trojan@1st.ch
authors.forename: Andreas
authors.initials: A
authors.lastname: Trojan
authors.forename: Athanasios
authors.initials: A
authors.lastname: Vergopoulos
authors.forename: Urs
authors.initials: U
authors.lastname: Breitenstein
authors.forename: Christoph
authors.initials: C
authors.lastname: Tausch
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Joechle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D016022:Case-Control Studies; D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000502:physiology*; D003915:Dextromethorphan / Q000378:metabolism; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D011960:Receptors, Estrogen / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6