Abstract
Background: Breast cancer is a major public health in Algeria. Tamoxifen has been approved for the treatment of ER+ breast cancer. Some of the 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 the 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 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 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 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 carriers of CYP2D6*1 allele (P<0.05).
Conclusion: Our results affirm 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 intended and lifestyle modifications can be implemented.
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