title: CYP2D6 and adjuvant tamoxifen: possible differences of outcome in pre- and post-menopausal patients.
abstract: OBJECTIVE
  Previous studies on CYP2D6 activity and the effect of adjuvant tamoxifen in breast cancer are inconsistent. We analyzed the impact of the CYP2D6 polymorphism in pre- and post-menopausal patients that were adherent to tamoxifen treatment for at least a year.
  
  
  METHODS
  A total of 382 breast cancer patients prescribed adjuvant tamoxifen for 5 years constituted the study-base. Clinical information, including compliance and outcome, was retrieved from medical records. Comprehensive CYP2D6 genotyping was performed and translated into predicted metabolic activity.
  
  
  CONCLUSIONS
  In patients adherent to tamoxifen for at least one year (n = 313) there was an association between reduced CYP2D6 activity (≤50% of normal) and recurrence (p = 0.025) and breast cancer-specific mortality (p = 0.034). In a multivariable analysis, CYP2D6 remained an independent predictor of outcome. In a subgroup analysis, the effect of CYP2D6 seemed to derive mainly from premenopausal patients, which represents a new finding that needs validation in a larger study sample. Original submitted 13 November 2012; Revision submitted 1 March 2013.
authors.affiliation: Department of Oncology & Pathology, Karolinska Institutet, Stockholm, Sweden. sara.margolin@karolinska.se
authors.forename: Sara
authors.initials: S
authors.lastname: Margolin
authors.forename: Jonatan D
authors.initials: JD
authors.lastname: Lindh
authors.forename: Linda
authors.initials: L
authors.lastname: Thorén
authors.forename: Hanjing
authors.initials: H
authors.lastname: Xie
authors.forename: Larissa
authors.initials: L
authors.lastname: Koukel
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Dahl
authors.forename: Erik
authors.initials: E
authors.lastname: Eliasson
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics; D011110:Polymorphism, Genetic; D017698:Postmenopause; D017697:Premenopause; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6