Zoledronat in der adjuvanten Therapie des rezeptornegativen Mammakarzinoms – Rationale und Erfahrungen mit Einzelfallentscheidungen

Zusammenfassung

Bereits frühe Untersuchungen zeigten einen Überlebensvorteil in Subgruppen durch die Bis­phos­phonat-Gabe bei metastasierten Patientinnen. Beim ossär metastasierten Mammakarzinom konnte durch die monatliche Zoledronat-Gabe eine Reduktion der Mortalität um 32 % erreicht werden [1]. Der vermutete Mechanismus besteht in der Veränderung des Mikromilieus von Tumorzellen, in apoptoseinduzierenden, antiangiogenetischen und antiadhäsiven Effekten [2] [3] [4] [5] [6] [7] . Hinzu kommt, dass Zoledronat die Interaktion zwischen Tumorzelle und Knochen bzw. Knochenmark stört. Der Knochenstoffwechsel wird herunter­reguliert, damit verschlechtern sich die Wachstumsbedingungen in einem Prädilektionsort der Metastasierung. All diese Effekte scheinen zunächst vom Rezeptorstatus und der Differenzierung der zugrunde liegenden Mammakarzinom­erkrankung unabhängig zu sein. Beim hormon­rezeptorpositiven Mammakarzinom besteht in der adjuvanten Behandlung mit Zoledronat zunehmende Datensicherheit bezüglich der Progress- und Rezidivprophylaxe unabhängig vom Menopausestatus. Obwohl Zoledronat derzeit in der adjuvanten Versorgung des Mammakarzinoms außerhalb der Zulassung eingesetzt wird, scheint diese Therapie über Studien hinaus bereits im klinischen Alltag etabliert zu sein. In der besonderen therapeutischen Situation beim ­triple- oder hormonrezeptornegativen Mammakarzinom mit ho­hem Rezidivrisiko wird zunehmend im Rahmen von Studien aber auch in einzelnen Fällen ebenfalls Zoledronat eingesetzt.

Abstract

Previous studies have already shown a survival benefit in sub groups of metastatic breast cancer treated with bisphosphonates. Zoledronate given monthly to patients with metastatic disease to the bones showed a reduction in mortality of 32 % [1]. Conceivable mechanisms include changes in the microenvironment of tumor cells, induction of apoptotic pathways, reduction of angiogenesis and cell adhesion [2] [3] [4] [5] [6] [7] . Moreover, zoledronate interferes with the interaction between tumor cells and the bone marrow microenvironment. Bone metabolism is reduced, and proliferation requirements are disrupted in a major target location of metastatic disease. All these effects seem to be independent of the estrogen receptor status or grading of the primary breast tumor. There is accumulating evidence that adjuvant treatment with zoledronate improves progression and recurrent free survival in estrogen receptor positive breast cancer independent of the menopausal status. Although the use of zoledronic acid in the adjuvant setting is still off label, it has become a major corner stone in everyday clinical practice. Moreover, also in the special situation of triple negative or estrogen receptor negative breast cancer with a high risk of recurrence, zoledronate is increasingly used both within clinical trials and in individual cases.

Schlüsselwörter

Triple negatives Mammakarzinom - Zoldronsäure - adjuvante Therapie - Falldiskussionen - Therapieempfehlung

Key words

Triple negative breast cancer - Zoldronat - adjuvant therapy - case discussion - therapy recommendation

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