Pharmakogenetik in der antihormonellen therapie von patientinnen mit einem mammakarzinom

The therapy of patients with breast cancer is still a challenge. Prognostic and predictive factors need to be identified in order to establish an individualized therapy. Recognized parameters are based on pathological characteristics of the tumour. Genetic variations can have an important influence on the course of disease and the efficacy and side effects of pharmaceuticals. In future, gene expression profiles could give reliable evidence about the prognosis. Genetic variations could also serve as predictive factor for clinical decisions. Pharmacogenetics assesses the pharmacodynamics and pharmacokinetics of drugs. The knowledge about genetic variations can provide the prediction of efficacy and side effects. It is known that enzymes of the steroid metabolism have numerous pharmacogenetic variations. There is evidence that polymorphisms in the CYP2D6 Gene might be associated with a decreased efficacy of tamoxifen that is equieffective to aromatase inhibitors. Concerning the pharmacogenetics of aromatase inhibition there are known polymorphisms of the CYP19A1 gene that are associated with altered peripheral sex hormone levels and altered prognosis in breast cancer patients. One study could even associate a polymorphism in the CYP19A1 gene with a prolonged time to progression in patients with metastatic breast cancer who have been treated with letrozole. Current studies analyse the influence of different genotypes on the efficacy and side effects of treatment with tamoxifen or aromatase inhibitors.