The Frequency of the Reduced Function CYP2D6*10 Allele and Its Impact on Clinical Outcomes in Syrian Breast Cancer Patients Treated with Tamoxifen

Background and objectives: CYP2D6 is the key enzyme responsible for tamoxifen bioactivation and is encoded by a highly complex and polymorphic gene, which may affect the activity of the enzyme; thus, the clinical outcomes of tamoxifen treatment. This study aimed at investigating the frequency of the reduced-function CYP2D6*10 allele (defined by 100C>T substitution) and evaluating the impact of 100C>T genotypes on breast cancer recurrence in Syrian breast cancer patients treated with tamoxifen.

Materials and methods: This observational case-control study encompassed breast cancer patients who received adjuvant tamoxifen therapy. CYP2D6*10 genotypes were investigated via sequencing the PCR amplicons of the CYP2D6 gene locus containing the 100C>T substitution. Disease-free survival (DFS) was used to evaluate the clinical outcomes. Kaplan-Meier method and Log-Rank tests were used to assess the relationship between genotypes and DFS.

Results: A total of 103 patients met the inclusion criteria; the case arm included 61 patients who had relapsed during five years since treatment commencement, while the control arm included 42 patients who completed recurrence-free five-year treatment. CYP2D6*10 presented at a frequency of 19.7% in the non-responders compared to 16.7% in the responders. No statistically significant differences were observed in the frequencies of the variant allele nor the 100C>T genotypes (CC, CT, and TT) between the two arms (P=0.585 and P=0.826, respectively). Our results revealed no statistically significant difference (P=0.912) in the median DFS among the three genotype groups.

Conclusions: Our study demonstrated no impact of CYP2D6*10 alone on the clinical outcomes of tamoxifen treatment in Syrian breast cancer patients heterozygous or homozygous for the variant allele, and the necessity to investigate other alleles (i.e., the *4 and *41) in order to integrate the data and explain the inter-individual discrepancies in the effectiveness of tamoxifen.