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Breast Cancer Research
Published in: Breast Cancer Research 4/2012

Open Access 01-08-2012 | Research article

Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival

Authors: Randi R Mathiesen, Elin Borgen, Anne Renolen, Erik Løkkevik, Jahn M Nesland, Gun Anker, Bjørn Østenstad, Steinar Lundgren, Terje Risberg, Ingvil Mjaaland, Gunnar Kvalheim, Per Eystein Lønning, Bjørn Naume

Published in: Breast Cancer Research | Issue 4/2012

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Abstract

Introduction

Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy (NACT) and to evaluate their prognostic impact.

Methods

Bone marrow and peripheral blood were collected before NACT (BM1: n = 231/PB1: n = 219), at surgery (BM2: n = 69/PB2: n = 71), and after 12 months from start of NACT (BM3: n = 162/PB3: n = 141). Patients were included from 1997 to 2003 and followed until 2009 (or ten years follow-up). DTC- and CTC-status were determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. The prognostic significance of DTCs/CTCs was assessed by univariate and multivariate Cox-regression analyses.

Results

Before NACT, DTCs and CTCs were detected in 21.2% and 4.9% of the patients, respectively. At surgery, 15.9% and 1.4% had DTC- and CTC-presence, compared to 26.5% and 4.3% at 12 months from start of NACT. Of patients for whom DTC results both before NACT and at 12 months were available, concordant results were observed in 68%, and 14 out of 65 had positive DTC-status at both time points. Presence of ≥ 1 DTC 12 months from start of NACT, but not at other time points, predicted reduced disease-free survival (DFS; HR 2.3, p = 0.003), breast cancer-specific survival (BCSS; HR 3.0, p < 0.001) and overall survival (OS; HR 2.8, p < 0.001). Before NACT, presence of ≥ 3 DTCs was also associated with unfavorable outcome, and reduced BCSS was observed for CTC-positive patients (HR 2.2, p = 0.046). In multivariate analysis, DTC status (</≥ 1 DTC) at 12 months after start of NACT remained as a prognostic factor for both DFS (HR 2.2, p = 0.005), BCSS (HR 2.6, p = 0.002) and OS (HR 2.6, p = 0.002). The survival for patients with change in DTC-status was determined by the DTC-status at 12 months.

Conclusion

Presence of DTCs after NACT indicated high risk for relapse and death, irrespective of the DTC-status before treatment. The results supports the potential use of DTC analysis as a monitoring tool during follow up, for selection of patients to secondary treatment intervention within clinical trials.
Appendix
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Metadata
Title
Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival
Authors
Randi R Mathiesen
Elin Borgen
Anne Renolen
Erik Løkkevik
Jahn M Nesland
Gun Anker
Bjørn Østenstad
Steinar Lundgren
Terje Risberg
Ingvil Mjaaland
Gunnar Kvalheim
Per Eystein Lønning
Bjørn Naume
Publication date
01-08-2012
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2012
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3242

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