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Clinical Study

Clinical utility of circulating tumour cell-based monitoring of late-line chemotherapy for metastatic breast cancer: the randomised CirCe01 trial



CirCe01 trial aimed to assess the clinical utility of circulating tumour cell (CTC)-based monitoring in metastatic breast cancer (MBC) patients beyond the third line of chemotherapy (LC).


CirCe01 was a prospective, multicentre, randomised trial (NCT01349842) that included patients with MBC after two systemic LC. Patients with ≥5 CTC/7.5 mL (CellSearch®) were randomised between the CTC-driven and the standard arm. In the CTC arm, changes in CTC count were assessed at the first cycle of each LC; patients in whom CTC levels predicted early tumour progression had to switch to a subsequent LC.


Greater than or equal to 5 CTC/7.5 mL were observed in N = 101/204 patients. In the CTC arm (N = 51), 43 (83%) and 18 (44%) patients completed CTC monitoring in the third and fourth lines, respectively, and 18 (42%) and 11 (61%) of these patients, respectively, had no CTC response. Thirteen (72%) and 5 (46%) of these patients underwent early switch to the next LC. Overall survival was not different between the two arms (hazard ratio = 0.95, 95% confidence interval = [0.6;1.4], p = 0.8). In subgroup analyses, patients with no CTC response who switched chemotherapy experienced longer survival than patients who did not.


Due to the limited accrual and compliance, this trial failed to demonstrate the clinical utility of CTC monitoring.

Clinical Trial Registration

NCT, NCT01349842,, registered 9 May 2011.

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Fig. 1: Design of the CirCe01 trial.
Fig. 2: Study flow chart.
Fig. 3: Survival.
Fig. 4: CTC level variation and protocol compliance at the third and fourth lines of chemotherapy.


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La Ligue Contre le Cancer, the French Ministry of Health and Institut Curie SIRIC2 programme.

Author information




L.C. and F.B. participated in data collection, data interpretation and statistical analyses, and wrote the manuscript. F.B. supervised data management and performed statistical analyses. P.C., E.B., D.L., H.B., E.D., S.C., N.K., S.L. and M.C. participated in the design of the study and included patients in the study. F.B. and S.C. coordinated data management and participated in statistical analyses. A.R. supervised the central laboratory for CTC detection. J.-Y.P. conceived the study, and participated in its design and coordination, and data interpretation and manuscript writing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Francois-Clement Bidard.

Ethics declarations

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki. This prospective, multicentre, open-label, randomised trial (six centres) was approved by the regional ethics board (Comité de Protection des Personnes—Ile de France) and identified as NCT01349842. All patients signed informed consent.

Data availability

The data that support the findings of this study are available from Institut Curie, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Institut Curie.

Competing interests

F.-C.B. and J.-Y.P. report grants and non-financial support from Menarini Silicon Biosystem, during the conduct of the study. M.C. reports personal fees and other from Novartis, during the conduct of the study; other from Sanofi, Servier, Abbvie, Accord and Astra Zeneca; personal fees from Lilly, outside the submitted work. The other authors have no disclosures.

Funding information

The trial was funded by grants from La Ligue Contre le Cancer and the French Ministry of Health (PHRC 2009 02-057). The circulating tumour biomarkers laboratory is supported by the Institut Curie SIRIC2 programme (grant INCa-DGOS-INSERM_12554).

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Cabel, L., Berger, F., Cottu, P. et al. Clinical utility of circulating tumour cell-based monitoring of late-line chemotherapy for metastatic breast cancer: the randomised CirCe01 trial. Br J Cancer 124, 1207–1213 (2021).

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