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Breast Cancer Research
Published in: Breast Cancer Research 5/2013

Open Access 01-10-2013 | Research article

The presence and prognostic impact of apoptotic and nonapoptotic disseminated tumor cells in the bone marrow of primary breast cancer patients after neoadjuvant chemotherapy

Authors: Andreas Daniel Hartkopf, Florin-Andrei Taran, Markus Wallwiener, Carsten Hagenbeck, Carola Melcher, Natalia Krawczyk, Markus Hahn, Diethelm Wallwiener, Tanja Fehm

Published in: Breast Cancer Research | Issue 5/2013

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Abstract

Introduction

Neoadjuvant systemic therapy of primary breast cancer (PBC) patients offers the possibility to monitor treatment response. However, patients might have metastatic relapse despite achieving a pathologic complete response (pCR). This indicates that local response to therapy must not be representative for systemic treatment efficacy. Therefore, the aim of this study was to compare local response with systemic tumor cell dissemination by determining the presence of disseminated tumor cells (DTCs), including apoptotic tumor cells, in the bone marrow (BM) of PBC patients after neoadjuvant chemotherapy (NACT).

Methods

DTCs were detected by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology (DTC status). The presence of apoptotic tumor cells was determined by using the M30 antibody (M30 status). This antibody detects a neo-epitope that is expressed only during early apoptosis.

Results

BM aspirates from 400 PBC patients that had completed NACT were eligible for this study. Of these, 167 (42%) patients were DTC positive (DTC status). The M30 status was investigated in 308 patients. Apoptotic (M30-positive) tumor cells were detected in 89 (29%) of these. Whereas the DTC status was not correlated (P = 0.557) to local treatment response (that is, pCR or a clinical complete/partial response), the presence of M30-positive tumor cells was significantly higher in patients that responded to therapy (P = 0.026). Additionally, DTC-positive patients were at an increased risk for disease relapse (hazard ratio, 1.87; 95% CI, 1.11 to 3.15; P = 0.019).

Conclusion

The presence of DTC is independent of therapy response of the primary tumor. As patients that are DTC positive after NACT have an unfavorable outcome, they might benefit from additional systemic treatment.
Appendix
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Metadata
Title
The presence and prognostic impact of apoptotic and nonapoptotic disseminated tumor cells in the bone marrow of primary breast cancer patients after neoadjuvant chemotherapy
Authors
Andreas Daniel Hartkopf
Florin-Andrei Taran
Markus Wallwiener
Carsten Hagenbeck
Carola Melcher
Natalia Krawczyk
Markus Hahn
Diethelm Wallwiener
Tanja Fehm
Publication date
01-10-2013
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2013
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3496

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