CYP2D6 polymorphisms and endoxifen concentration in Chinese patients with breast cancer

Abstract

Background

The plasma concentration of endoxifen, the active metabolite of tamoxifen, might be affected by different CYP2D6 genotypes in patients with breast cancer, but solid evidence is still lacking in Asian patients. This prospective study aimed to investigate the relationship between CYP2D6 genetic polymorphisms and endoxifen plasma concentrations among Chinese patients with breast cancer treated with tamoxifen.

Methods

From August 2015 to June 2018, 110 patients with breast cancer were enrolled. CYP2D6 variant alleles and endoxifen plasma concentration were determined using Sanger sequencing and high-performance liquid chromatography-tandem mass spectrometry, respectively.

Results

The most frequent allele of CYP2D6 was *10 (56.4%). The most frequent genotype of CYP2D6 was *10/*10 (33%), *1/*10(28.2%) and *2/*10(14.5%). Sixty-four patients (58.2%) were Normal Metabolizers (NM), while 46 (41.8%) were Intermediate Metabolizers (IM). All patients except two had endoxifen concentrations above the threshold of 5.9ng/ml. The median endoxifen plasma concentrations for patients with CYP2D6 genotypes *1/*2 and *1/10 were higher compared to other genotypes (p = 0.012). The median endoxifen plasma concentration was higher in NM than in IM (18ng/ml vs. 13ng/ml, p = 0.0077). Patients with CYP2D6*10(T/T) had lower endoxifen concentrations than those with *10(C/T) and *10(C/C) but the difference was not significant. There were no significant differences in adverse events between patients in the NM and IM groups or between patients with the CYP2D6*10 (T/T) genotype and non-*10 (T/T) genotype.

Conclusion

Only CYP2D6 IMs and NMs were identified in this study. Almost all patients had the endoxifen concentrations above the threshold. The endoxifen plasma concentration was lower in CYP2D6 IMs than in NMs, but these variants did not compromise the adverse effects of tamoxifen in Asian patients with breast cancer.

Trial registration

The study protocol was approved by the institutional review boards of Sun YatSen University Cancer Center (Ethics approval number, B201506501,20160115).