Aromatasehemmer riskant für das Gehirn?

Zusammenfassung

Die Erfolge der endokrinen Therapiemöglichkeiten beim metastasierenden Brustkrebs sind beeindruckend. Die adjuvante endokrine Therapie befindet sich momentan im Wandel. Soll weiter wie seit 30 Jahren Tamoxifen eingesetzt werden oder Aromatasehemmer bis 5 oder mehr Jahre? Ehe eine großzügige Umstellung erfolgt, sind mögliche längerfristige Nachteile auf das ZNS zu klären. Das Enzym Aromatase sichert die elementare Östrogenversorgung der Neuronen in vielen Hirnregionen. Bei komplett inhibierter Östrogensynthese durch einen Aromatasehemmer lässt die Synapsenplastizität im Hippocampus nach. Neurobiologisch erklärbar ist das durch fehlende neuroprotektive Östrogeneffekte. Das kann neurodegenerative Veränderungen mit Lern- und Gedächtnisproblemen bewirken. Daher ist multizentrisch zu klären, ob längerfristig Aromatasehemmer für das Gehirn riskant sind. Bisher wurde kein deutlich längeres Überleben unter Aromatasehemmer gegenüber Tamoxifen nachgewiesen. Die Aromataseforschung weist auf mögliche Neurodegeneration hin - evtl. längerfristig bis zum Alzheimer-Risiko.

Abstract

Impressive successes have been achieved with the possibilities offered by the endocrinal treatment of metastasizing breast cancer. Adjuvant endocrinal therapy is presently undergoing a change. Should we continue to prescribe tamoxifen as we have been doing for the past 30 years, or should we resort to administering aromatase inhibitors for up to five or more years? Before initiating a large-scale change we should make every effort to find out whether there would be any long-term adverse effects on the central nervous system. The enzyme aromatase safeguards elementary oestrogen supply to the neurons in the brain region. If an aromatase inhibitor completely blocks oestrogen synthesis, there will be an decline of synapsis plasticity in the hippocampus. This can be explained neurologically by absence of neuroprotective effects exercised by the oestrogens and may trigger neurodegenerative changes associated with difficulties of learning and memory. Hence, it is mandatory to clarify multicentrically whether long-term administration of aromatase inhibitors involves brain risks. So far there has been no indication of a definitely longer survival due to administration of aromatase inhibitors than with tamoxifen. Aromatase research indicates possible neurodegeneration, possibly with long-term effects leading finally to Alzheimer's disease.

Schlüsselwörter

Tamoxifen - Aromatasehemmer - adjuvante Brustkrebstherapie - Neuroprotektion - Alzheimer-Risiko

Key words

Tamoxifen - aromatase inhibitor - adjuvant endocrinal therapy - neuroprotection - neurodegeneration - risk of Alzheimer's disease

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