Open Access Highly Accessed Research article

Serial enumeration of circulating tumor cells predicts treatment response and prognosis in metastatic breast cancer: a prospective study in 393 patients

Markus Wallwiener12*, Sabine Riethdorf3, Andreas Daniel Hartkopf4, Caroline Modugno1, Juliane Nees1, Dharanija Madhavan5, Martin Ronald Sprick6, Sarah Schott2, Christoph Domschke2, Irène Baccelli56, Birgitt Schönfisch4, Barbara Burwinkel25, Frederik Marmé12, Jörg Heil2, Christof Sohn2, Klaus Pantel3, Andreas Trumpp56 and Andreas Schneeweiss12

Author Affiliations

1 National Center for Tumor Diseases, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany

2 Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany

3 Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany

4 Department of Obstetrics and Gynecology, University of Tübingen, Calwerstraße 7, 72076 Tübingen, Germany

5 Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

6 Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

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BMC Cancer 2014, 14:512  doi:10.1186/1471-2407-14-512

Published: 11 July 2014



To prospectively assess circulating tumor cell (CTC) status at baseline (CTCBL) and after one cycle of a new line of systemic therapy (CTC1C), and changes from CTCBL to CTC1C (CTC kinetics, CTCKIN) for their utility in predicting response, progression-free (PFS) and overall survival (OS) in metastatic breast cancer (MBC).


CTCBL and CTC1C status was determined as negative (-) or positive (+) for < 5 or ≥ 5 CTCs/7.5 ml blood using CellSearch™ (Veridex). CTCKIN was categorized as favorable (CTC1C-) or unfavorable (CTC1C+). Tumor response was to be assessed every 2–3 months using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Statistical analysis focused on the relation between CTC status and CTCKIN, and response, PFS, and OS.


133/393 (34%) patients enrolled were CTCBL+. CTC1C status after one cycle and radiological tumor response were assessed after median (range) periods of 1.2 (0.5–3.2) and 2.9 (0.5–4.8) months, respectively. 57/201 (28%) were CTC1C+. Median [95% confidence interval] PFS and OS (months) were significantly reduced in CTCBL+ vs. CTCBL- patients (PFS 4.7 [3.7–6.1] vs. 7.8 [6.4–9.2]; OS 10.4 [7.9–15.0] vs. 27.2 [22.3–29.9]), and for CTC1C+ vs. CTC1C- patients (PFS 4.3 [3.6–6.0] vs. 8.5 [6.6–10.4]; OS 7.7 [6.4–13.9] vs. 30.6 [22.6–not available]). Unfavorable CTCKIN was significantly associated with progressive disease. Multivariate Cox regression analysis revealed prognostic factors for shorter PFS (CTCBL+, persistent CTCs after one cycle, ≥ 3rd-line therapy, and triple-negative receptor status) and shorter OS (CTCBL+, persistent CTCs after one cycle, bone-and-visceral/local metastases, ≥ 3rd-line therapy, and triple-negative receptor status).


CTCBL, CTC1C, and CTCKIN are predictive of outcome in MBC. Serial CTC enumeration is useful in tailoring systemic treatment of MBC.

Trial registration

Not applicable.

Metastatic breast cancer; Circulating tumor cells; Systemic therapy; Treatment response; Survival