title: CYP2D6 polymorphisms influence tamoxifen treatment outcomes in breast cancer patients: a meta-analysis.
abstract: OBJECTIVE
  To evaluate whether breast cancer (BC) patients with CYP2D6 gene variation have different clinical tamoxifen (TAM) treatment outcomes to those with normal function of CYP2D6.
  
  
  METHODS
  Systematic searches of the PubMed up to February 21, 2013, were retrieved. The study end points were disease-free survival (DFS) and overall survival (OS). Fixed or random-effects meta-analytical models were used to calculate summary hazard ratio (HR) and corresponding 95 % confidence intervals (CIs). Meta-regression, Galbraith plots, subgroup analysis, and sensitivity analysis were also performed.
  
  
  RESULTS
  A total of 11,701 BC patients from 20 trials were included. Compared with reduced CYP2D6 function, normal function was associated with a trend toward improved DFS (HR = 1.37, 95 % CI 1.12-1.69, P = 0.002) and OS (HR = 1.25, 95 % CI 1.03-1.50, P = 0.021). We found significant heterogeneity between studies. When the analysis was stratified into subgroups, significantly worse DFS was found in the groups of intermediate metabolizer versus extensive metabolizer (HR = 1.65, 95 % CI 1.04-2.64, P = 0.035), Asian population (HR = 3.29, 95 % CI 1.64-6.63, P = 0.001), 5 years TAM treatment duration (HR = 1.59; 95 % CI 1.14-2.22, P = 0.006), concomitant chemotherapy (HR = 1.35, 95 % CI 1.04-1.76, P = 0.025), and TAM alone (HR = 1.44, 95 % CI 1.44-2.06, P = 0.045). With respect to OS, no significant association was demonstrated in stratified analyses.
  
  
  CONCLUSIONS
  We concluded that CYP2D6 polymorphisms may influence tamoxifen treatment outcomes of DFS in BC patients.
authors.affiliation: Department of Geriatrics, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zeng
authors.forename: Yanqiong
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Liu
authors.forename: Jianpeng
authors.initials: J
authors.lastname: You
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Qiliu
authors.initials: Q
authors.lastname: Peng
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Ruolin
authors.initials: R
authors.lastname: Li
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.forename: Xue
authors.initials: X
authors.lastname: Qin
mesh_terms: D000483:Alleles; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D044466:Asian People; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D016016:Proportional Hazards Models; D017594:Publication Bias; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6