CYP2D6 Genotype and Risk of Recurrence in Tamoxifen Treated Breast Cancer Patients

Abstract

<b>Background:</b> Despite consistent pharmacogenetic effects of CYP2D6 on tamoxifen exposure, there isconsiderable controversy regarding the validity of CYP2D6 as a predictor of tamoxifen outcome. Understandingthe current state of evidence in this area and its limitations is important for the care of patients who requireendocrine therapy for breast cancer. Materials and <br/><b>Methods</b>: A total of 101 patients with breast cancer whoreceived tamoxifen therapy for at least 3 years, were genotyped for common alleles of the CYP2D6 gene bynested-PCR and restriction fragment length polymorphism PCR. Patients were classified as extensive or poormetabolizers (PM) based on CYP2D6*4 alleles in 3 different groups according to the menopause, Her2-neustatus, and stage 3. <br/><b>Results</b>: The mean age of the patients with the disease recurrence was 50.8±6.4 and in nonrecurrent patients was 48.2±6.8. In this study 63.3% (n=64) patients were extensive metabolizers and 36.6%(n=37) were poor metabolizers. Sixty four of the 101 patients (63.3%) were Her2-neu positive. For tamoxifentreatedpatients, no statistically significant difference in rate of recurrence observed between CYP2D6 metabolicvariants in stage 3 and post-menopausal patients. However, there was a significant association between CYP2D6genotype and recurrence in tamoxifen-treated Her2-neu positive patients. Compared with other women withbreast cancer, those with Her2-neu positive breast cancer and extensive metabolizer alleles had a decreasedlikelihood of recurrence. <br/><b>Conclusions</b>: This study for the first time demonstrated significant effects of CYP2D6extensive metabolizer alleles on risk of recurrence in Her2-neu positive breast cancer patients receiving adjuvanttamoxifen therapy. Therefore, CYP2D6 metabolism, as measured by genetic variation, can be a predictor ofbreast cancer outcome in Her2-neu positive women receiving tamoxifen.