Table 2. Clinical relevance of CTC in metastatic BC.

CTC detection	Number of patients	Clinical relevance – conclusions	References
CellSearch assay	177 MBC patients	CTC represent an independent prognostic factor for PFS and OS in patients with metastatic BC. The number (⩾5) of CTC at baseline and at the first follow-up visit were the most significant predictors of PFS and OS.	Cristofanilli et al, 2004
AdnaTest BreastCancer	39 MBC patients (226 blood samples)	A major proportion of CTC of metastatic BC patients shows EMT and tumour stem cell characteristics.	Aktas et al, 2009
CellSearch assay vs AdnaTest BreastCancer	254 MBC patients	The rate of BC patients with HER-2-negative primary tumours but HER-2-positive CTC was 32% using the CellSearch and 49% using the AdnaTest BreastCancer.	Fehm et al, 2010
CellSearch assay	235 MBC patients median follow-up: 18 months	The prognostic information provided by CTC count may be useful in patient stratification and therapy selection, particularly in the CTC-positive group, in which various therapeutic choices may procure differential palliative benefit.	Giuliano et al, 2011
CellSearch assay	517 MBC patients	Risk of death increased linearly with increasing CTC count in all molecular tumour subtypes, but was higher in ER+ and triple-negative MBC than in HER2+. CTC' prognostic effect was less evident in HER2+ MBC patients treated with targeted therapy.	Giordano et al, 2012
Double immunofluorescence (Ariol system)	25 MBC and 25 early BC patients	CTC expressing Twist and vimentin, suggestive of EMT, were identified. EMT is involved in the metastatic potential of CTC.	Kallergi et al, 2011
Various systems	Meta-analysis (1990–2012), n=3069	Detection of CTC is a reliable prognosticator in patients with metastatic BC: PFS: HR 1.78, 95% CI 1.52–2.09; OS: HR 2.33, 95% CI 2.09–2.60.	Zhang et al, 2012
CellSearch and AdnaTest Breast Cancer	254 MBC patients	The prognostic relevance of CTC detection in metastatic BC patients depends on the test method.	Muller et al, 2012
CellSearch assay	267 MBC patients	Elevated CTC before the second cycle was an early predictive marker of poor PFS and OS, and could be used to monitor treatment benefit CTC decrease under treatment was stronger with targeted therapy.	Pierga et al, 2012

Abbreviations: BC=breast cancer; CI=confidence interval; CTC=circulating tumour cell; DFS=disease-free survival; EMT=epithelial–mesenchymal transition; ER=oestrogen receptor; HR=hazard ratio; MBC=metastatic BC; OS=overall survival; PFS=progression-free survival; PR=progesterone receptor; RT-qPCR=reverse-transcriptase quantitative PCR.