IMPACT OF CYP2D6 POLYMORPHISMS IN PREDUCTING OCCURRENCE OF ADVERSE EFFECT TO TAMOXIFEN AND DEVELOPING RECCURENCE IN ER+ BREAST CANCER PATIENETS:

Objectives: Breast cancer is a major public health in Algeria. Tamoxifen has been approved in the treatment of ER+ breast cancer. Some of negative side effects of tamoxifen are frequently a reason for discontinuation of therapy during treatment, which would otherwise be potentially lifesaving. In the current study, we assessed the association between CYP2D6 polymorphisms and tamoxifen efficacy in Algerian population receiving tamoxifen as adjuvant therapy in ER+ breast cancer. Methods: A total of 76 Algerian hormone receptor-positive premenopausal breast cancer patients with adjuvant tamoxifen treatment were investigated (45.36±6.13). DNA genotyping was performed by TaqMan Open Array technology. Tamoxifen and its metabolites levels were measured by ultra-high-performance liquid chromatography (UHPLC) followed by electro spray tandem mass spectrometry (LC-MS/MS). Results: A significant association between the presence of deficit copy of enzyme activity and development of adverse effect after the commencement of tamoxifen therapy. Low plasma endoxifen were observed in patients categorized as (NM/PM), (IM/ IM), (IM/PM) and (PM/PM). Patients with increased plasma endoxifen concentrations were significantly more likely than patients with reduced or null activity to not report recurrences (P<0.05). We realized that the combination genotypes NM/PM, IM/IM, IM/PM, with PM/PM were more strongly associated with disease recurrence and adverse effects than NM carries of CYP2D6*1 allele (P<0.05). Conclusion: Our results affirm that CYP2D6 polymorphism should be considered in predicting the occurrence of adverse effect fatty liver in women treated with tamoxifen. Thus, alternative treatment can be intended and lifestyle modifications can be implemented