Are plasma concentrations of tamoxifen active metabolites sufficient to ensure therapeutic efficacy for tamoxifen treated women with breast cancer in Poland?

Abstract

Tamoxifen is the most commonly used drug for treating those patients with breast cancer who are oestrogen receptor positive. The main active metabolite of tamoxifen is (Z)-endoxifen whose therapeutic efficacy depends on its plasma concentration. A therapeutically effective threshold level has indeed been defined for (Z)-endoxifen above which the breast cancer relapse rate is significantly reduced. Such steady-state concentrations are conditional on gene polymorphism, principally cytochrome P450 2D6 ( CYP2D6 ), that modulates the activity of the encoded enzymes that convert tamoxifen to its active metabolites. This drug’s metabolism however may become significantly altered when other medication is concomitantly taken, such as selective serotonin reuptake inhibitors, which inhibit CYP2D6. A recent study have demonstrated that the majority of tamoxifen treated women with breast cancer in Poland, may not in fact attain the therapeutic threshold levels of (Z)-endoxifen. In such cases, personalising optimal treatment should be based on direct monitoring of steady-state plasma concentrations of tamoxifen and its metabolites, which can thereby significantly improve therapeutic efficacy.