| Background It shows that CYP2D6 function is important in the conversion of tamoxifen to its active metabolites. CYP2C9, CYP2C19, CYP2C8, CYP2B6, CYP3A4, CYP3A5, CYP1A2, CYP2A6 and SULT1A1 were also involved in the process. Previous studies accessing the association of CYP2C19 with outcomes of patients using tamoxifen for breast cancer have yielded conflicting results. Through the prognosis study of 132 patients with breast cancer, Okishiro et al. found that there is no association between disease-free recurrence of breast cancer patients and the CYP2C19 genotype of the patients. But Ruiter et al., through a study of 80 breast cancer patients who received tamoxifen, found that the survival of breast cancer patients with CYP2C19*2 is higher than that of breast cancer patients with wild-type CYP2C19. Zafra-Ceres et al. demonstrated that CYP2C19*2 can serve as a predictive factor for survival in breast cancer patients treated with tamoxifen in the Spanish population. These studies suggest that CYP2C19 polymorphism is also a factor that affects the efficacy of tamoxifen. Schroth suggested that CYP2C19*17 may be a predictive factor in breast cancer patients who used tamoxifen. But Moyer didn’t think so.Objective The aim of this meta-analysis was to get a more precise conclusion of CYP2C19, and to clarify the effects of them on the survival of the breast cancer patients using tamoxifen.Methods A systematic search of PubMed, Embase, Cochrane, CBM, CNKI was performed, comparing patients with or without CYP2C19*2 and CYP2C19*17. Two investigators independently performed data according to the included studies. Any disagreement was resolved by the responsible investigator. Summary the data of disease-free survival(DFS) and overall survival(OS) were used to assess the association between the CYP2C19 genotype and the survival in breast cancer patients. All meta-analyses were conducted with STATA version 12.0 (StataCorp LP, College Station, TX, USA). The I2 statistic was used to assess between-study statistical heterogeneity, We performed subgroup analysis by genotypes. For evaluating the influence of the results, Sensitivity analyses were based on the evaluation results of the literature as well as the quality characteristics of each study. Publication biases were evaluated by funnel plot.Results Six studies met the inclusion criteria, including 787 breast cancer patients. Two studies had high methodological quality of studies; three studies had moderate methodological quality of studies; one study had low methodological quality of study. The meta-analysis reveals that:1. The integrated OR on the association between CYP2C19 and DFS, calculated by random-effect model, was 0.54 (95%CI= 0.34-0.84, P= 0.013), with a moderate heterogeneity(I2= 68.3%).2. The pooled results of two studies for OS was OR= 0.46 (95%CI= 0.21-1.01, P= 0.233), with a moderate heterogeneity(I2= 29.7%).3. Subgroup analysis showed that both CYP2C19*2 and CYP2C19*17 were associated with increased survival. Pooling of data from CYP2C19*2 show toward to increase survival of disease with OR of 0.25 (95%CI-0.14-0.43). No heterogeneity was found among the different studies. (I= 0%, p= 0.934). The data from CYP2C19*17 show toward to increase survival of disease with OR of 0.74 (95%CI= 0.56-0.96). With a low heterogeneity(I2= 18.6%, p= 0.293).Conclusions This meta-analysis suggests that the CYP2C19*2 and CYP2C19*17 genotypes are associated with increased survival in breast cancer patients after using tamoxifen. However, this study included a small number of limited sample size, some studies methodological quality is not high, and the evidence should be applied with caution. |
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