CYP2D6 gene polymorphism had a profound impact upon the effect of tamoxifen as adjuvant endocrine therapy in breast cancers. However, it had never been reported whether the adverse drug reactions vary by CYP2D6 metabolic status for patients treated with tamoxifen or toremifene. We conducted an retrospective study in breast cancer patients to investigate the impact of CYP2D6 metabolizers on liver dysfunction events, gynecological events, and dyslipidemia events. According to CYP2D6*10 (100C → T) genotype, the enrolled patients were further categorized into four cohorts (extensive metabolizers taking tamoxifen [EM + TAM], extensive metabolizers taking toremifene [EM + TOR], intermediate metabolizers taking tamoxifen [IM + TAM], intermediate metabolizers taking toremifene cohort [IM + TOR]). A total of 192 patients were included into the study, with a median follow-up time of 26.2 months. In EM + TAM cohort, the risks of liver dysfunction events (P = 0.004) and gynecological events (P = 0.004) were significantly higher compared with EM + TOR cohort. In IM + TAM cohort, the risks of liver dysfunction events (P = 0.14) and gynecological events (P = 0.99) were not significantly different from IM + TOR cohort. Significant decrease of total cholesterol was observed in EM + TAM cohort around 1 year after taking tamoxifen (P < 0.001). Significant interactions between CYP2D6 metabolic status and endocrine agents were observed in terms of liver dysfunction events (p-interaction = 0.007) and gynecological events (p-interaction = 0.026). These findings suggested that CYP2D6 gene polymorphism played a significant role in predicting liver dysfunction, gynecological diseases and lipid metabolism changes among patients taking tamoxifen or toremifene.

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