Disseminated tumor cells in bone marrow and circulating tumor cells in blood of breast cancer patients: current state of detection and characterization.

Despite the progress resulting from early detection and improved adjuvant therapy, the prognosis of breast cancer patients is still limited by the occurrence of distant metastases largely due to clinically occult micrometastases that remain undetected at primary diagnosis even by high-resolution imaging approaches. Recent research efforts have concentrated on the identification of additional parameters allowing individual risk assessment and stratification of patients for targeted therapies, since traditional prognostic factors are not sufficient to predict metastatic relapse and treatment decisions are still mainly based on statistical risk parameters. Highly sensitive and specific immunocytochemical and molecular assays now enable the detection and characterization of disseminated and circulating tumor cells (DTCs and CTCs, respectively) at the single cell level in bone marrow (BM) and peripheral blood, providing insights into the first crucial steps of the metastatic cascade. However, because of the still high variability of results in DTC/CTC detection, the necessity of standardized approaches will be discussed. A large number of studies showed that the presence of DTCs in BM has prognostic impact for primary breast cancer patients. DTCs are likely to escape from chemotherapy by maintaining a dormant nonproliferating state. There is also evidence for a stem cell-like phenotype of DTCs, probably contributing to the opportunity to escape from dormancy control and to start expansion to manifest metastases. Blood would also be an ideal source for the detection and monitoring of CTCs because of an easy noninvasive sampling procedure enabling repeated analyses. While prognostic significance of CTCs could be reliably demonstrated for metastatic breast cancer, studies to analyze the impact of CTCs in primary breast cancer patients and the potential to replace or supplement BM analysis are still ongoing. Furthermore, molecular characterization of CTCs might contribute to improving targeted and more individualized cancer therapies.