Does Increasing The Daily Tamoxifen Dose In Patients With Diminished Cyp2d6 Activity Increase Toxicity?

561 Background: Tamoxifen treated breast cancer patients with diminished CYP2D6 activity have lower endoxifen exposure, which may lead to inferior treatment outcomes. Increasing the daily tamoxifen dose from 20 mg to 40 mg increases endoxifen in CYP2D6 poor (PM) and intermediate (IM) metabolizing patients. We previously reported that endoxifen exposure of an IM pt receiving 40 mg is similar to that of an extensive or ultra-rapid metabolizer (EM/UM) receiving 20 mg, while a PM at 40 mg continues to have lower exposure. Here we investigated whether increasing the dose to 40 mg/day in CYP2D6 PM and IM increases treatment toxicity. Methods: Patients receiving 20 mg tamoxifen for ≥ 4 months who were not taking a strong CYP2D6 inhibitor were genotyped for CYP2D6 using the Amplichip CYP450 test (Roche Diagnostics, Indianapolis, IN). PM and IM were increased to 40 mg for 120 days while EM/UM remained on 20 mg. Toxicity data was collected on the ordinal FACT-B Endocrine Subscale (0: “not at all” to 4 “very much”) ...