Circulating tumor and endothelial cells as predictors of response in metastatic breast cancer

The detection of microscopic disease is associated with prognostic implications in primary breast cancer [1]. In metastatic breast cancer (MBC), reliable detection of circulating tumor cells (CTCs) has been obtained using immunomagnetic separation and subsequent analysis by the CellSpotter™ analyzer (Veridex LLC, a Johnson & Johnson company, Warren, NJ, USA) [2, 3]. This technology is becoming a standard tool for the 'real-time' assessment of prognosis and response to treatment [4, 5]. The detection of CTCs in patients with MBC about to start a new line of treatment has been shown to predict progression-free survival and overall survival and treatment benefit. The prognostic value was independent of the line of therapy (for example, first line versus second line or more) [2, 3]. Moreover, in multivariate analysis CTCs demonstrated superior value compared with the site of metastasis (for example, visceral versus soft tissue/bone), type of therapy, and length of time to recurrence after definitive primary surgery. Furthermore, the prognostic value of CTCs has been shown to be superior to standard tumor markers (for example, Ca27-29), tumor burden and phenotype of disease [6]. We have recently focused on determining the feasibility of the genotypic characterization of CTCs and correlating with the expression of similar genes in primary or metastatic lesions [7].

Increases in the number of circulating endothelial cells (CECs) and progenitors (CEPs) have been reported in various pathological conditions including cancer [8, 9]. At the clinical level, evidence is emerging that CEC kinetics and viability might correlate with clinical outcomes in cancer patients who undergo anti-angiogenic treatment [10]. The CellSpotter™ analyzer is also being investigated for measurement and characterization of CEC [11]. Therefore, CEC and CEP measurement has potential as a surrogate marker for monitoring anti-angiogenic treatment and drug activity, and could help to determine the optimal biological dose of anti-angiogenic drugs, which are being used with increasing frequency in medical oncology.