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Clinical Significance of Occult Metastatic Cells in Bone Marrow of Breast Cancer Patients

^a Frauenklinik und Poliklinik, Technische Universität München, Klinikum rechts der Isar, München, Germany; ^b Molekulare Onkologie, Universitäts-Frauenklinik, Universitätsklinikum Eppendorf, Hamburg, Germany

Correspondence: Klaus Pantel, M.D., Ph.D., Universitäts-Frauenklinik, Universitätsklinikum Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. Telephone: 49-40-42803-3503; fax: 49-40-42803-5379; e-mail: pantel{at}uke.uni-hamburg.de

The early and clinically occult spread of viable tumor cells to the organism is increasingly considered a hallmark in cancer progression, as emerging data suggest that these cells are precursors of subsequent distant relapse. Using monoclonal antibodies to epithelial cytokeratins or tumor-associated cell membrane glycoproteins, individual carcinoma cells can be detected on cytologic bone marrow preparations at frequencies of 10^–5 to 10^–6. Prospective clinical studies have shown that the presence of these immunostained cells in bone marrow, as a frequent site of overt metastases, is prognostically relevant with regard to relapse-free and overall survival. This screening approach may be, therefore, used to improve tumor staging and guide the stratification of patients for adjuvant therapy in clinical trials. Another promising application is monitoring the response of micrometastatic cells to adjuvant therapies, which, at present, can only be assessed retrospectively after an extended period of clinical follow-up. The present review summarizes the current data on the clinical significance of occult metastatic breast cancer cells in bone marrow.

Key Words. Breast cancer • Bone marrow • Cytokeratin • Prognosis • Survival

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