Impact of CYP2D6 Polymorphisms on Predicting the Adverse Effects of Tamoxifen and Recurrence in ER+ Breast Cancer Patients

Abstract

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