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Annals of Oncology Advance Access published online on October 22, 2009
Annals of Oncology, doi:10.1093/annonc/mdp391
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Single circulating tumor cell detection and overall survival in nonmetastatic breast cancer

F.-C. Bidard1,2, C. Mathiot1,3, S. Delaloge4, E. Brain5, S. Giachetti6, P. de Cremoux1,7, M. Marty6 and J.-Y. Pierga1,2,8,*

1 CirCe laboratory, Institut Curie, Paris
2 Department of Medical Oncology, Institut Curie, Paris
3 Hematology laboratory, Institut Curie, Paris
4 Department of Medical Oncology, Institut Gustave Roussy, Villejuif
5 Department of Medical Oncology, Centre René Huguenin, Saint Cloud
6 Department of Medical Oncology, Hôpital Saint Louis, Paris
7 Pharmacology laboratory, Institut Curie, Paris
8 University Paris Descartes, Paris, France

* Correspondence to: Prof. J.-Y. Pierga, Institut Curie, 26 rue d'Ulm, 75005 Paris, France. Tel: +33-1-44-32-44-07; Fax: +33-1-53-10-40-41; E-mail: jean-yves.pierga{at}curie.net

Background: Circulation of cancer cells in the blood is a mandatory step for metastasis, but circulating tumor cells (CTC) have a low metastatic efficiency in preclinical animal models. In this prospective study, we reported the clinical outcome of nonmetastatic breast cancer patients according to CTC detection.

Patients and methods: In 115 nonmetastatic patients diagnosed with large operable or locally advanced breast cancer, we prospectively detected CTC using the CellSearch system before and after neoadjuvant chemotherapy in a phase II trial (REMAGUS02).

Results: At baseline, 23% of patients were CTC positive, but only 10% had >1 CTC/7.5 ml of blood. After a median follow-up of 36 months, CTC detection before chemotherapy was an independent prognostic factor for both distant metastasis-free survival [DMFS; P = 0.01, relative risk (RR) = 5.0, 95% confidence interval (CI) 1.4–17] and overall survival (OS; P = 0.007, RR = 9, 95% CI 1.8–45). CTC detection after chemotherapy was of less significance (P = 0.07 and 0.09, respectively). Moreover, CTC detection showed interesting characteristics as an individual predictive test for metastatic relapses (sensibility 55%, specificity 81%, and global accuracy 77%).

Conclusions: Detection of ≥1 CTC/7.5 ml before neoadjuvant chemotherapy can accurately predict OS. Our findings may change the clinical management of nonmetastatic breast cancer and indicate that the metastatic efficiency of CTC could be higher than previously reported.

breast cancer, circulating tumor cells, neoadjuvant chemotherapy, prognosis

Received for publication June 29, 2009. Accepted for publication July 6, 2009.


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