CYP2D6 polymorphisms influence the efficacy of adjuvant tamoxifen in Thai breast cancer patients

Abstract

Aim: We evaluated single nucleotide polymorphisms (SNPs) of CYP2D6 to identify those that influence the efficiency of tamoxifen in adjuvant treatment of breast cancer through a matched case-control study.

Methods: Peripheral blood DNA was collected from 20 patients with disease recurrence during adjuvant tamoxifen treatment and from 19 patients who had completed 5 years of tamoxifen therapy without recurrence of breast cancer. CYP2D6*4 (1846G > A; rs3892097), CYP2D6*10 (100C > T, rs1065852), and CYP2D6*5 (deletion) were genotyped. The correlation between disease-free survival (DFS) and genotype and clinical outcome were assessed using Kaplan-Meier analysis and a log-rank test.

Results: We found the allelic frequency of CYP2D6*10 during this study. Patients with the CYP2D6*10 homozygous variant T/T genotype had a significantly shorter median of DFS than those with C/T (P = 0.036), but DFS was not significantly different from that of patients with the C/C genotype (P = 0.316). One patient who was a carrier both of CYP2D6 G/A (1846G > A) and T/T (100C > T) had DFS of 22.7 months.

Conclusions: This study demonstrated that CYP2D6*10/*10 was significantly associated with shorter DFS in Thai breast cancer patients receiving tamoxifen. This was a pilot study investigating the correlation of CYP2D6 polymorphisms and their influence on clinical outcomes in Thai estrogen receptor-positive breast cancer patients.

Keywords: CYP2D6 polymorphism; breast cancer; pharmacogenetics; single-nucleotide polymorphism (SNP); tamoxifen.

Figure 1

Kaplan–Meier estimates of disease-free survival (DFS) with the CYP2D6*10 genotype in 39 Thai breast cancer patients receiving tamoxifen treatment. Patients with the CYP2D6*10 homozygous variant T/T genotype were compared with patients with heterozygous C/T (A) or homozygous wild-type C/C genotype (B) and heterozygous C/T compared with homozygous wild-type C/C genotype (C).