Abstract
Abstract Background: Only few studies have investigated the issue of breast cancer patients’ adherence to tamoxifen therapy and factors influencing adherence behavior. Especially in the context of different CYP2D6 genotypes adherence to tamoxifen has not been extensively studied yet. Variations in the CYP2D6 genotype, as well as patients taking inhibitors of CYP2D6 (e.g. antidepressants) contribute to different side effects and adherence rates to adjuvant tamoxifen. Materials and Methods: 106 premenopausal breast cancer patients who met inclusion criteria were consecutively included in the study at the outpatient unit of the Department of Gynecology, Innsbruck Medical University. Within their routine after care appointment patients completed a comprehensive PRO assessment including the FACT-B/ES, the HADS and a self-report questionnaire on adherence behavior (SMAQ). The multi-method approach comprised the Simplified Medication Adherence Questionnaire, a semi-structured interview, physicians’ ratings and blood levels for tamoxifen metabolites. Additionally, the CYP2D6 genotype was determined in all patients participating in this part of the study. Results: 19% patients were poor metabolizer (PM), 51% intermediate metabolizer (IM), 29% extensive metabolizer (EM) and 7% ultra-rapid metabolizer (UM). Significant group differences with regard to tamoxifen and endoxifen serum concentrations were found between the metabolization groups (p=0.044). UMs had the lowest tamoxifen and highest endoxifen concentrations. Only 3.2% of the patients analyzed had no measurable tamoxifen concentrations in their serum. All non-compilant patients were from the extensive metabolizer group. However, during follow-up 25% (2/6) of patients with UM genotype, 13% (4/30) with EM genotype, 1% (1/50) with IM genotype and 0% (0/19) with the PM genotype discontinued their tamoxifen therapy due to therapy related side effects. In addition anti-depressants were more frequently prescribed in the extensive metabolizer group leading to lower levels of the active metabolite endoxifen. Conclusion: A trend towards higher hot flashes was observed in the EM and UM group. We did not find significant differences in QOL between CYP2D6 metabolizing groups. Trend level significance was found for global QOL (on a descriptive level) physical well-being and emotional well-being. Non-adherence to tamoxifen therapy is more frequent in patients with CYP2D6 EM and UM genotype. These preliminary data may explain part of the current controversy over CYP2D6 genotype predicting response to tamoxifen and suggest that patients most likely to benefit from tamoxifen are paradoxically most likely to stop their tamoxifen therapy prematurely. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-02-04.
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