Micrometastatic disease in breast cancer: clinical implications.

The presence of bone marrow disseminated tumour cells (DTCs) was shown to predict poor clinical outcome in early breast cancer. However, peripheral blood is easier to obtain and allows for serial monitoring of minimal residual disease. Towards this aim, circulating tumour cells (CTCs) in the blood are detected using either direct methods, mainly antibody-based assays (immunocytochemistry, immunofluorescence and flow cytometry), or indirect methods, mainly nucleic acid-based assays (detection of mRNA transcripts by reverse transcriptase polymerase chain reaction, RT-PCR). The detection of CTCs using RT-PCR for CK19 was shown to be an independent prognostic factor in women with early breast cancer. Furthermore, considerable progress has been accomplished in genotyping, phenotyping and profiling micrometastatic cells. The challenge now is to integrate minimal residual disease as a prognostic and predictive tool in the management of breast cancer. This requires the standardisation of micrometastatic cell detection and characterisation, which will allow the incorporation of CTCs/DTCs into prospective clinical trials testing their clinical utility.