Open Access Highly Accessed Research article

The prognostic significance of tumour cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients

Timothy J Molloy1, Astrid J Bosma1, Lars O Baumbusch23, Marit Synnestvedt4, Elin Borgen5, Hege Giercksky Russnes5, Ellen Schlichting4, Laura J van't Veer1 and Bjørn Naume46*

Author Affiliations

1 Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands

2 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Postboks 4953, Nydalen, 0424 Oslo, Norway

3 Biomedical Research Group, Department of Informatics, University of Oslo, Postboks 4953, Nydalen, 0424 Oslo, Norway

4 Division of Surgery and Cancer Medicine, Oslo University Hospital Radiumhospitalet, Postboks 4953, Nydalen, 0424 Oslo, Norway

5 Department of Pathology, Oslo University Hospital Radiumhospitalet, Postboks 4953, Nydalen, 0424 Oslo, Norway

6 Institute of Clinical Medicine, University of Oslo, Postboks 4953, Nydalen, 0424 Oslo, Norway

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Breast Cancer Research 2011, 13:R61  doi:10.1186/bcr2898

Published: 14 June 2011

Abstract

Introduction

The detection of circulating tumour cells (CTCs) in the peripheral blood and disseminated tumour cells (DTCs) in the bone marrow are promising prognostic tools for risk stratification in early breast cancer. There is, however, a need for further validation of these techniques in larger patient cohorts with adequate follow-up periods.

Methods

We assayed CTCs and DTCs at primary surgery in 733 stage I or II breast cancer patients with a median follow-up time of 7.6 years. CTCs were detected in samples of peripheral blood mononuclear cells previously stored in liquid-nitrogen using a previously-developed multi-marker quantitative PCR (QPCR)-based assay. DTCs were detected in bone marrow samples by immunocytochemical analysis using anti-cytokeratin antibodies.

Results

CTCs were detected in 7.9% of patients, while DTCs were found in 11.7%. Both CTC and DTC positivity predicted poor metastasis-free survival (MFS) and breast cancer-specific survival (BCSS); MFS hazard ratio (HR) = 2.4 (P < 0.001)/1.9 (P = 0.006), and BCSS HR = 2.5 (P < 0.001)/2.3 (P = 0.01), for CTC/DTC status, respectively). Multivariate analyses demonstrated that CTC status was an independent prognostic variable for both MFS and BCSS. CTC status also identified a subset of patients with significantly poorer outcome among low-risk node negative patients that did not receive adjuvant systemic therapy (MFS HR 2.3 (P = 0.039), BCSS HR 2.9 (P = 0.017)). Using both tests provided increased prognostic information and indicated different relevance within biologically dissimilar breast cancer subtypes.

Conclusions

These results support the use of CTC analysis in early breast cancer to generate clinically useful prognostic information.