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Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells

Tanja Fehm1 email, Oliver Hoffmann2 email, Bahriye Aktas2 email, Sven Becker1 email, Erich F Solomayer1 email, Diethelm Wallwiener1 email, Rainer Kimmig2 email and Sabine Kasimir-Bauer2 email

Department of Gynecology and Obstetrics, Calwer Straße 7, University Hospital of Tuebingen, D-72076 Tuebingen, Germany

Department of Gynecology and Obstetrics, Hufelandstraße 55, University Hospital of Essen, D-45122 Essen, Germany

author email corresponding author email

Breast Cancer Research 2009, 11:R59doi:10.1186/bcr2349

Published: 10 August 2009


See related editorial by Schmitt and Foekens, http://breast-cancer-research.com/content/11/5/109

Abstract

Introduction

The role of circulating tumor cells (CTCs) in blood of primary breast cancer patients is still under investigation. We evaluated the incidence of CTCs in blood, we evaluated the correlation between CTCs and disseminated tumor cells (DTCs) in the bone marrow (BM), and we characterized CTCs for the expression of HER2, the estrogen receptor (ER) and the progesterone receptor (PR).

Methods

Blood of 431 patients with primary breast cancer were analyzed for EpCAM, MUC1 and HER2 transcripts with the AdnaTest BreastCancer™ (AdnaGen AG, Germany). Expression of the ER and PR was assessed in an additional RT-PCR. BM aspirates from 414 patients were analyzed for DTCs by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3.

Results

DTCs were found in 107/414 patients (24%), CTCs were detected in 58/431 (13%) patients. DTCs were associated with PR status of the primary tumor (P = 0.04) and CTCs significantly correlated with nodal status (P = 0.04), ER (P = 0.05), and PR (P = 0.01). DTCs in the BM weakly correlated with CTCs (P = 0.05) in blood. Interestingly, the spread of CTCs was mostly found in triple-negative tumors (P = 0.01) and CTCs in general were mostly found to be triple-negative regardless of the ER, PR and HER2 status of the primary tumor.

Conclusions

(1) Due to the weak concordance between CTCs and DTCs the clinical relevance may be different. (2) The biology of the primary tumor seems to direct the spread of CTCs. (3) Since the expression profile between CTCs and the primary tumor differs, the consequence for the selection of adjuvant treatment has to be evaluated.


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