Die klinische Bedeutung des Nachweises von isolierten Tumorzellen im Knochenmark und peripheren Blut von Patientinnen mit primärem Mammakarzinom

Zusammenfassung

Trotz wesentlicher Fortschritte in der systemischen Therapie des Mammakarzinoms und deutlicher Prognoseverbesserung sind Rezidive nach oft langer Latenzzeit für diese Erkrankung charakteristisch. Ausgangspunkt für eine Fernmetastasierung sind in der Regel isolierte Tumorzellen, die bereits früh im Verlauf der Erkrankung hämatogen disseminieren. Der Nachweis dieser minimalen Tumorresiduen (minimal residual disease, MRD) ist mit konventionellen bildgebenden Verfahren nicht möglich. Der immunzytochemische Nachweis isolierter Tumorzellen im Knochenmark ist die am besten etablierte Methode, um Tumorresiduen zu detektieren. Die daraus gewonnenen Informationen über Prävalenz und Phänotyp der Tumorzellen lassen Rückschlüsse auf Tumorbiologie und individuelle Prognose zu, und könnten in Zukunft in der adjuvanten Situation zu einer Optimierung der Therapie führen. Die immunzytochemische Untersuchung des Knochenmarkes könnte die Beantwortung der von Patientinnen häufig gestellten Frage nach dem individuellen Erfolg adjuvanter Therapien in Zukunft erleichtern und Grundlage für die Einleitung einer „sekundär-adjuvanten Therapie“ im Rahmen der onkologischen Nachsorge sein. Außerhalb von klinischen Studien sollte der Nachweis von isolierten Tumorzellen allerdings derzeit nicht als Grundlage für eine Therapieentscheidung herangezogen werden.

Abstract

Minimal residual disease (MRD), i.e., isolated tumor cells (ITC) in bone marrow, may be the source of potentially fatal overt distant metastases in solid tumors even several years after primary treatment. MRD can be detected by immunohistochemical methods, using antibodies directed against cytokeratins, cell-surface markers, or molecular, PCR-based techniques. Among solid tumors, the clinical relevance of MRD has been most extensively studied in breast cancer patients. Recently, the highest level of evidence for the prognostic impact of MRD in primary breast cancer was reached by a pooled analysis comprising more than 4000 patients, showing poor outcomes in patients with MRD at primary therapy. Yet clinical application of MRD detection is hampered by the lack of a standardized detection assay. Moreover, clinical trial results demonstrating the benefit of therapeutic interference based on bone marrow status are still lacking. Recent results suggest that in addition to its prognostic impact, MRD can be used for therapy monitoring or as a potential therapeutic target after phenotyping of the tumor cells. Persisting MRD after primary treatment may lead to an indication for extended adjuvant therapy. However, until the clinical consequences of MRD detection in solid tumors and particularly in breast cancer have been validated, the detection of isolated tumor cells in bone marrow should be performed mainly in clinical trials.

Schlüsselwörter

Mammakarzinom - disseminierte Tumorzellen - isolierte Tumorzellen - Mikrometastasen - minimale Tumorresiduen - adjuvant - sekundär‐adjuvant

Key words

breast cancer - disseminated tumor cells - isolated tumor cells - micrometastases - minimal tumor residues - adjuvant - secondary adjuvant

Literatur

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