Selection of patients who will likely respond or will develop relevant side effects has the potential to improve anticancer therapy. Considering the many contributing factors in drug disposition,... Show moreSelection of patients who will likely respond or will develop relevant side effects has the potential to improve anticancer therapy. Considering the many contributing factors in drug disposition, we hypothesized that variability in drug disposition could be better explained by phenotype, rather than by the genotype alone. In this thesis, phenotype tests in oncology were studied, with a focus on phenotype breath tests and CYP2D6 metabolism in breast cancer patients using tamoxifen. A review is given of phenotype studies published before 2011 addressing drug metabolizing enzymes in relation to anticancer drugs. The 13C-dextromethorphan-breath test was related to CYP2D6 genotype and serum concentrations of endoxifen, the active metabolite of tamoxifen. A 13C-dextromethorphan breath test was equally predictive of endoxifen levels as compared to the CYP2D6 genotype. We showed that there was no difference in CYP2D6 phenotype between metastasized patients and early breast cancer patients. Because endoxifen levels did not significantly differ between the two groups as well, our findings do not have clinical implications thus far. Show less
Currently, 35-45% of newly diagnosed breast cancer patients in developed countries is aged 65 years and older. Older women with breast cancer comprise a heterogeneous group due to large differences... Show moreCurrently, 35-45% of newly diagnosed breast cancer patients in developed countries is aged 65 years and older. Older women with breast cancer comprise a heterogeneous group due to large differences with regard to concomitant diseases, physiological reserve and functional status. Current guidelines for breast cancer are based on studies that were mostly performed in younger patients. Therefore, treatment of older women with breast cancer is not evidence-based, and it cannot be expected that clinical trials will fill this gap of knowledge in the near future. The aim of this thesis was to investigate several aspects of breast cancer treatment in older women. In Part I, several aspects of treatment in older breast cancer patients were assessed. Part II assessed methodological aspects of studying breast cancer in older patients. This thesis has shown that older patients are at increased risk for overdiagnosis of breast cancer due to population screening, with potential harmful effects due to the increased risk of complications of treatment. Despite changing treatment strategies, breast cancer prognosis of older women has not improved. Current treatment strategies and decisions tools are insufficient. Observational studies will become increasingly important in this patient population, the use of accurate methods will be essential. Show less
