Minimal residual cancer and its clinical relevance

Abstract

About one third of axillary node-negative breast cancer patients will develop distant metastases, even if there was no evidence of tumor spread beyond the breast at the time of primary diagnosis. Several studies support the hypothesis that the presence of hematogenous disseminated tumor cells (DTC) in the bone marrow of cancer patients, a condition known as minimal residual disease (MRD), can be regarded as a precursor of clinically manifest distant metastases. MRD can be detected either as DTC in the bone marrow or as circulating tumor cells (CTC) in the peripheral blood. Bone marrow and peripheral blood represent mesenchymal compartments with rare prevalence of epithelial cells without evidence of malignant disease. There are two main approaches for the detection of DTC and/or CTC: 1) immunologic assays using monoclonal antibodies against epithelium-specific proteins, and 2) polymerase chain reaction-based molecular methods detecting tissue-specific transcripts. Although data on the prognostic relevance of DTC in bone marrow are vast, data on the prognostic role of CTC are much less convincing. Sampling peripheral blood instead of bone marrow, however, might enhance the therapeutic implications of detecting MRD in breast cancer, a topic that is examined in this article. This article also examines the major quality criteria for the transfer of new markers into the clinical routine in relation to MRD and reviews whether and in what detail MRD in bone marrow meets these criteria.