Tamoxifen

patients with CYP2D6 variants, which are associated with reduced enzyme activity, have a lower endoxifen concentration. In some studies, this is associated with an increased risk of recurrence of the disease [1] [2]. The gene for CYP2D6 has many variants, which lead to different metabolic phenotypes. A distinction is made between a normal metabolizer (NM), an ultra rapid metabolizer (UM) with greatly increased enzyme activity, an intermediate metabolizer (IM) with reduced enzyme activity and a poor metabolizer (PM) with no enzyme activity. These metabolic types occur at different frequencies depending on the population. For example, the frequency of poor metabolizers in the Caucasian population is around 5-10% and for intermediate metabolizers around 10-15% [1]. In CYP2D6 poor metabolizers, tamoxifen is not or only insufficiently converted into the active ingredient endoxifen and patients can therefore not build up a sufficient active level [3]. The CPIC (Clinical Pharmacogenetic Implementation Consortium) dosage guideline recommends the choice of an alternative hormone therapy for CYP2D6 IM or PM [1].

• Before starting tamoxifen therapy
• To clarify the molecular cause of insufficient endoxifen levels under tamoxifen therapy.

In the case of CYP2D6 intermediate or poor metabolizers and based on the activity score, an alternative hormone therapy, e.g. GnRH analogues plus aromatase inhibitors, or the maximum approved dose for tamoxifen should be discussed.