The effect of a tamoxifen dose increase from 20 mg to 40 mg in patients with at least one inactive CYP2D6 variant allele and/or concomitant use of a CYP2D6 inhibitor.

584 Background: Genetic polymorphisms leading to reduced CYP2D6 activity and the use of CYP2D6 inhibitors both influence the formation of endoxifen (active metabolite of tamoxifen (TAM)). CYP2D6 genotyping is not part of the standard clinical management of patients treated with TAM and there are no formal recommendations for dose adjustments in patients using TAM and a CYP2D6 inhibitor. We hypothesized that in patients who are either a CYP2D6 intermediate or poor metabolizer and/or are treated with a CYP2D6 inhibitor a dose adjustment of TAM compensates for reduced formation of endoxifen. Methods: Female breast cancer patients treated with TAM 20mg QD for at least 4 weeks were included. They were genotyped for CYP2D6 variant alleles (inactive alleles *3, *4, *5, *6 and decreased activity alleles *10, *41). Patients with at least one inactive allele, two decreased CYP2D6 activity alleles, and/or concomitant use of a CYP2D6 inhibitor received a dose increase of TAM to 40mg QD for 4 weeks. TAM, 4-OH-TAM, N-d...