Author details

6. Limitations of current methods for CTC detection

be evaluated.

52 Breast Cancer and Surgery

Therapy monitoring

Treatment selection based on CTCs

Modified after Ref. [33].

7. Conclusions

ence and phenotype/genotype of CTCs (Table 2).

Prognostication Yes; CTCs are significantly associated with diseasefree and overall survival

Table 2. Clinical role of CTCs in early and metastatic breast cancer.

neoadjuvant treatment

Potential Early BC Metastatic BC

Unclear; presence of CTCs 2 years after completion of chemotherapy predicts worse survival; contradictory results with regard to association between CTC changes and response to

Possibly relevant; evidence pending (clinical trials: TREAT CTC, active, closed to patient entry)

In this context, one needs to keep the limitations of current methods for CTC detection in mind. Epithelial cell adhesion molecule (EpCAM)-dependent enrichment techniques are the most widely used with the CellSearch™ system being so far the only FDA-approved system [30]. However, detection of CTCs is limited by the CellSearch™ system to cells with expression of EPCAM and cytokeratin 8/18/19. Respectively, the CellSearch system can certainly miss the detection of subpopulations of CTCs with decreased epithelial marker expression as a result of CTCs that have undergone epithelial-mesenchymal transition (EMT) [31]. It was observed that tumor cells which already initiated EMT are correlated with worse prognosis and therapy resistance [32]. Therefore, many EpCAM-independent methods are currently being developed and tested for CTC characterization. Translation into clinical routine practice of these new methods seems to be currently difficult. Multicenter assessment studies are lacking, and thus their reproducibility, sensitivity and specificity remain to

Circulating tumor cells are currently considered one of the most promising biomarkers for prediction of survival and monitoring of therapy in solid malignancies. While their prognostic significance has long been proven in early and metastatic breast cancer, further research is urgently needed to examine the possibility of guiding treatment decisions based on the pres-

> Yes (level I evidence); high CTC levels correlate with shorter progression-free and overall survival

> Possibly relevant; High CTC levels after start of first-line chemotherapy can adequately predict progression; however, patients do not benefit from a switch to another regimen (clinical trials: SWOG

Possibly relevant; evidence pending (ongoing clinical trials: STIC CTC METABREAST, DETECT

(cut-off: 5 CTCs/7.5 ml PB)

0500, ongoing: CirCe01)

III/IVa/IVb/V)

Malgorzata Banys-Paluchowski<sup>1</sup> \*, Florian Reinhardt<sup>2</sup> and Tanja Fehm2

\*Address all correspondence to: banys.malgorzata@yahoo.com

1 Department of Gynecology and Obstetrics, Marienkrankenhaus Hamburg, Hamburg, Germany

2 Department of Gynecology and Obstetrics, University Hospital Duesseldorf, University of Duesseldorf, Duesseldorf, Germany
