Impact of CYP2D6 Polymorphisms on Tamoxifen Responses of Women with Breast Cancer: A Microarray-based Study in Thailand

This study was designed to investigate the frequency of CYP2D6 polymorphisms and evaluate the associationbetween genetic polymorphisms of CYP2D6 and tamoxifen therapeutic outcome in Thai breast cancer patients.We recruited 48 breast cancer patients who received adjuvant tamoxifen for evaluating CYP2D6 geneticpolymorphisms using microarray-based technology. Associations between genotypes-phenotypes and diseasefree survival were analyzed. Median follow up time was 5.6 years. The mean age of the subjects was 50 years.The 3 common allelic frequencies were 43.8% (*10), 36.5 (*1) and 10.4% (*2) which are related to extensivemetabolizer (EM) and intermediate metabolizer (IM) with 70.8% and 29.2 %, respectively. No associationbetween CYP2D6 genotypes and DFS was demonstrated. Nevertheless, exploratory analysis showed statisticallysignificant shorter DFS in the IM group of post-menopause patients (HR, 6.85; 95% CI, 1.48 –31.69; P = 0.005).Furthermore, we observed statistically significant shorter DFS of homozygous CYP2D6*10 when comparedwith heterozygous CYP2D6*10 and other genotypes (P=0.005). CYP2D6*10 was the most common genotype inour subjects. Post-menopause patients with homozygous CYP2D6*10 and IM have shorter DFS. To confirm thisrelationship, larger samples and comprehensively designed trials in Thailand are required.