Tamoxifen Resistance and CYP2D6 Copy Numbers in Breast Cancer Patients


Background: Breast cancer accounts about one million from total annual ten million new diagnosed casesof neoplasia worldwide and is the main cause of death due to cancer in women. Tamoxifen is the most popularselective estrogen receptor modulator used in anti estrogen treatments. Tamoxifen must be converted into itsmetabolite endoxifen for biologic effects; this conversion process is catalysed by highly polymorphic cytochromeP450 2D6 (CYP2D6). This study surveyed copy number variation of the CYP2D6 gene and its possible correlationwith Tamoxifen resistance in breast cancer patients.
Methods: This case control study was performed on samplestaken from 79 patients with breast cancer who used tamoxifen in Yazd and Tehran Cities, Iran. Real time reactionswere conducted for 10 healthy samples using the comparative Ct (Cycles threshold) method, each pair of genesbeing compared and samples with ratios around 1 were taken as control samples. Proliferation reactions weredone by Real-Time PCR ABI Prism 7500. All registered data were transformed into SPSS 15 program andanalyzed.
Results: Efficiency of PCR for both CYP2D6 and ALB genes was 100%. From all 23 drug resistantpatients 21.7% had one copy, 47.8% two copies and 30.4% had three copies. Also from all 56 drug sensitivepatients, 26.8% had one copy, 51.8% two copies and 21.4% had three copies. The percentage of patients withone and two copies was similar between two groups but patients with three copies were more likely to belong tothe drug resistant group more. Odd ratios for one and two copies were 0.759 and 0.853 respectively, indicatingpossible protective effects while that for three copies was 1.604.
Conclusions: Based on our study there is nosignificant link between CYP2D6 gene copy numbers and tamoxifen resistance in women with breast cancer.But more studies considering other influencing factors appear warranted.