CYP2D6 polymorphisms and the therapeutic outcome with Tamoxifen therapy in breast cancer patients from Kosovo

Selvete Shuleta-Qehaja,Aleksandar Dimovski,Aleksandra Kapedanovska Nestorovska,Ljubica Shuturkova,Zoran Sterjev,Petar Stefanovski,Zorica Naumovska

doi:10.33320/maced.pharm.bull.2018.64.02.004

Abstract

Tamoxifen is a selective estrogen receptor modulator (SERM) used for the prevention of breast cancer and for the treatment of metastatic and early stage receptor positive breast cancer. It has been shown than tamoxifen is metabolized by the cytochrome P450 2D6 (CYP2D6) enzymes, especially with the CYP26 isoform. The aim of this study was to examine the prevalence of CYP2D6*4, CYP2D6*9 and CYP2D6*10 variants in patients with breast cancer in Kosovo as well as the association between CYP2D6 polymorphisms and the therapeutic outcome in tamoxifen treated patients. The study included 111 patients who were at the age of 25 to 70 years (45.75 ± 9.50). The overall variant allele frequency of CYP2D6*4 was 0.16. The genotypic frequencies of the CYP2D6*4 polymorphism in all patients were 0.02 for *4/*4, 0.28 for *1/*4 and 0.70 for the *1/*1 genotype. The overall CYP2D6*10 variant allele frequency was 0.30 and the frequency of *10/*10, *1/*10 and *1/*1 genotypes was 0.11, 0.37 and 0.52, respectively. In our study, a population of the CYP2D6∗9 variant allele was not detected. In addition, we did not find any correlation between the evaluated genotypes for CYP2D6 polymorphisms and the therapeutic outcome with tamoxifen therapy. Although our study is a rather small- scale compared to large multicentre studies, we believe that it will contribute to determining the impact of CYP2D6 polymorphisms on the success of tamoxifen therapy in patients with a diagnosed breast cancer. Our results are pointing to the direction of the growing number of claims that there is still no strong evidence of any therapeutic connection between the polymorphisms examined and the outcome of the therapy. Keywords: Tamoxifen, breast cancer, CY2D6*4, CYP2D6*9, CYP2D6*10

Highlights

In women, breast cancer is the most common cancer diagnosed in both more and less developed regions, withS
In order to evaluate the association between cytochrome P450 2D6 (CYP2D6) polymorphisms and therapeutic outcome we divided the patients into two groups: patients with the disease and the second group consisted of patients with a stable condition of the illness
CYP2D6 is involved in the metabolism of 20–25% of clinically used drugs and exhibits a clinically relevant gene polymorphism that modifies the pharmacokinetics of nearly 10% of the drugs used (Pinto & Dolan, 2011)

Summary

Introduction

Breast cancer is the most common cancer diagnosed in both more and less developed regions, with. Intensive epidemiological, clinical, and genetic studies have identified a number of biological and social traits as risk factors associated with breast cancer. The first and foremost among them is the evidence of BRCA1 and BRCA2 susceptibility genes, familial history of breast cancer, age, higher socioeconomic status, ionizing radiation, life span length, alcohol consumption, and a variety of hormone and metabolic factors. A relevant etiological function has been ascribed to elevated levels of estrogens, their active metabolites, and androgens (Muti et al, 2006)

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