Disseminated Tumor Cells as Biomarkers for Breast Cancer

Abstract

Owing to the difficulty in obtaining bone marrow, peripheral blood would clearly be a more convenient sample site for detection of disseminated tumor cells, which, once they are detected in peripheral blood, are described as circulating tumor cells. However, one of the challenges of peripheral blood ana lysis is that the yield of these cells in peripheral blood is known to be quite low and none of the published studies has yet demonstrated their prognostic relevance at the early stage of disease. One of the possible reasons for the higher frequency in bone marrow may be that the bone marrow vasculature acts as a filter due to its unique sinusoidal system. Another reason for the lower rate of detection of circulating tumor cells could be the limitations of current methodologies. Owing to the advantages of using peripheral blood, technical advances to increase the yield of circulating tumor cells have received more attention in recent years. Automated peripheral blood ana lysis by CellSearch (Veridex, NJ, USA), where enrichment and staining are performed in an automated and closed system, without human intervention, represents one of the technical advances in recent years allowing the field to move forwards. Nowadays, the ana lysis of peripheral blood samples of early-stage breast cancer patients is performed as standard in clinical trials, and will serve as a good platform for evaluation of the prognostic significance of circulating tumor cells at this stage. This analytical platform is, so far, the only FDA-approved method for the detection of circulating tumor cells, restricted to metastatic breast cancer patients. By employing the CellSearch ana lysis for the detection of circulating tumor cells in metastatic breast cancer patients, not only could the prognostic significance of circulating tumor cells be demonstrated, but also their suitability as biomarkers for the monitoring of therapeutic response [5]. Breast cancer represents a leading cause of morbidity and mortality in women, mainly due to the propensity of the primary tumors to metastasize [1]. The metastases occur either through continuous spread of the tumor cells from the primary tumor or through invasion of the cells into lymph and blood vessels, where they spread to lymph nodes or distant organs. Once metastases are detected by conventional diagnostic methods, disease is regarded as metastatic and, thus, incurable. For several decades, efforts have been made to define a useful biomarker for early metastatic spread. One of the surrogate markers of early hematogenous metastatic spread is disseminated tumor cells, known in literature as minimal residual disease, minimal residual cancer, occult metastases and micrometastases [2]. Technologies for the detection of disseminated tumor cells have evolved based on the detection of epithelial markers in the nonepithelial background. After enrichment of target cells, the detection is usually carried out either by means of immunohistochemistry or molecular approaches.