CYP2D6 polymorphisms influence tamoxifen treatment outcomes in breast cancer patients: a meta-analysis

Cancer Chemother Pharmacol. 2013 Aug;72(2):287-303. doi: 10.1007/s00280-013-2195-9. Epub 2013 May 28.

Abstract

Purpose: 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.

Publication types

  • Review

MeSH terms

  • Alleles
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Asian Continental Ancestry Group
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cytochrome P-450 CYP2D6 / genetics*
  • Disease-Free Survival
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Phenotype
  • Polymorphism, Genetic / genetics*
  • Proportional Hazards Models
  • Publication Bias
  • Survival Analysis
  • Tamoxifen / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • Tamoxifen
  • Cytochrome P-450 CYP2D6