Association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome of breast cancer after tamoxifen adjuvant endocrine therapy in Chinese population

Abstract

Tamoxifen is the most widely used adjuvant endocrine therapy for breast cancer. However, the pharmacogenetic effect of CYP2D6 on its efficacy remains unclear. Therefore, this study aimed to evaluate the association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome in Chinese breast cancer patients. A total of 72 tamoxifen-treated early breast cancer patients were included in this study. CYP2D6*10 (c.100C>T) polymorphisms (C/C: wild type; T/T: homozygous mutant genotype T; C/T: heterozygote genotype C) were detected by pyrosequencing. The plasma concentrations of tamoxifen and its two major active metabolites were determined by liquid chromatography tandem mass spectrometry (LC-MS). Disease-free survival (DFS) and overall survival (OS) were assessed by Kaplan-Meier analysis, while the Cox proportional hazards model was used in multivariate tests for prognostic significance. We found that T/T carrier showed the lowest serum concentration of endoxifen as compared to C/C and C/T carriers (p<0.01). In the subgroup of patients below 40 years of age, T/T carriers appeared to have the shortest DFS and OS as compared to other genotype carriers (p<0.01). When genotypes (C/C, C/T and T/T carriers) and other clinical characteristics were adjusted, tumor size (>2 cm) and grades were independent prognostic factors for DFS but not OS (tumor size >2 cm: HR: 3.870, 95% CI: 1.045-14.330, P = 0.043; tumor grades: HR: 2.230, 95% CI: 1.090-4.562, P = 0.028). In conclusion, the T/T genotype is a negative prognostic factor in young breast cancer patients using tamoxifen. Tumor size (>2 cm) and grades are independent prognostic factors for DFS, when genotype of CYP2D6*10 (c.100C>T) is adjusted.

Keywords: CYP2D6; breast cancer; genotyping; tamoxifen.

Figures

Figure 1

DFS of genotype C/C, C/T and T/T carriers. Log-rank test showed that the T/T carrier had worse DFS than the C/C and C/T carriers (χ2 = 8.371, P = 0.015) in the subgroup of patients below 40 years of age.

Figure 2

OS of genotype C/C, C/T and T/T carriers. Log-rank test showed that the T/T carrier had worse OS than the C/C and C/T carriers (χ2 = 8.347, P = 0.015) in the subgroup of patients below 40 years of age.