Breast Cancer Research and Treatment

, Volume 124, Issue 2, pp 403–412 | Cite as

HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial

  • Tanja Fehm
  • Volkmar Müller
  • Bahriye Aktas
  • Wolfgang Janni
  • Andreas Schneeweiss
  • Elmar Stickeler
  • Claus Lattrich
  • Christian R. Löhberg
  • Erich Solomayer
  • Brigitte Rack
  • Sabine Riethdorf
  • Christoph Klein
  • Christian Schindlbeck
  • Kerstin Brocker
  • Sabine Kasimir-Bauer
  • Diethelm Wallwiener
  • Klaus Pantel
Clinical trial


There is a growing body of evidence that HER2 status can change during disease recurrence or progression in breast cancer patients. In this context, re-evaluation of HER2 status by assessment of HER2 expression on circulating tumor cells (CTCs) is a strategy with potential clinical application. The aim of this trial was to determine the HER2 status of CTCs in metastatic breast cancer patients comparing two CTC assays. A total of 254 patients with metastatic breast cancer from nine German university breast cancer centers were enrolled in this prospective study. HER2 status of CTCs was assessed using both the FDA-approved CellSearch® assay and AdnaTest BreastCancer™. Using the CellSearch assay, 122 of 245 (50%) patients had ≥5 CTCs, and HER2-positive CTCs were observed in 50 (41%) of these patients. Ninety of 229 (39%) patients were CTC positive using AdnaTest BreastCancer, and HER2 positivity rate was 47% (42 of 90). The rate of breast cancer patients with HER2-negative primary tumors but HER2-positive CTCs was 32% (25 of 78) and 49% (28 of 57) using the CellSearch assay and AdnaTest BreastCancer, respectively. Considering only those patients who had CTCs on both tests (n = 62), concordant results regarding HER2 positivity were obtained in 50% of the patients (31/62) (P = 0.96, κ = −0.006). HER2-positive CTCs can be detected in a relevant number of patients with HER2 negative primary tumors. Therefore, it will be mandatory to correlate the assay-dependent HER2 status of CTCs to the clinical response on HER2-targeted therapies.


Breast cancer Circulating tumor cells HER2 Metastasis 





Circulating tumor cell




Food and drug administration


Human epidermal growth factor receptor 2


Epithelial cell adhesion molecule


Estrogen receptor


Fluorescence in situ hybridization


Fluorescein isothiocyanate




Mucin 1


Not available


Progesterone receptor


Reverse transcriptase polymerase chain reaction



This work was supported by an unrestricted research grant of Roche Pharma AG, Germany. Furthermore, this study was partly supported by Adnagen (Langenhagen, Germany). We thank Cornelia Coith, Susanne Hoppe, Sylke Krenkel, Oliver Mauermann, Malgorzata Stoupiec, and Silke Dürr-Störzer for excellent technical assistance. Our special thanks to Ute Hilcher for coordinating the study. In addition, we would like to thank all doctors (Michaela Becker, Julia Jüstock, Dina Mury, Mitras Tewes, and Julia Zeitz) for help with patients and data collection, Dr. Elke Heidrich-Lorsbach (Alcedis GmbH) for statistical analysis and data management, and Lee Miller from Miller Medical Communications for editing and reviewing the manuscript.


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Tanja Fehm
    • 1
  • Volkmar Müller
    • 2
  • Bahriye Aktas
    • 3
  • Wolfgang Janni
    • 4
  • Andreas Schneeweiss
    • 5
  • Elmar Stickeler
    • 6
  • Claus Lattrich
    • 7
  • Christian R. Löhberg
    • 8
  • Erich Solomayer
    • 9
  • Brigitte Rack
    • 10
  • Sabine Riethdorf
    • 11
  • Christoph Klein
    • 12
  • Christian Schindlbeck
    • 10
  • Kerstin Brocker
    • 5
  • Sabine Kasimir-Bauer
    • 3
  • Diethelm Wallwiener
    • 1
  • Klaus Pantel
    • 11
  1. 1.Department of Gynecology and ObstetricsUniversity of TübingenTübingenGermany
  2. 2.Department of GynecologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  3. 3.Department of Gynecology and ObstetricsUniversity Hospital of EssenEssenGermany
  4. 4.Department of Gynecology and ObstetricsUniversity of DüsseldorfDüsseldorfGermany
  5. 5.Department of Gynecology and ObstetricsUniversity of HeidelbergHeidelbergGermany
  6. 6.Department of Gynecology and ObstetricsUniversity of FreiburgFreiburgGermany
  7. 7.Department of Gynecology and ObstetricsUniversity of RegensburgRegensburgGermany
  8. 8.Department of Gynecology and ObstetricsUniversity of ErlangenErlangenGermany
  9. 9.Department of Gynecology and ObstetricsUniversity of HomburgHomburg/SaarGermany
  10. 10.Department of Gynecology and ObstetricsUniversity of MunichMünchenGermany
  11. 11.Institute of Tumor BiologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  12. 12.Institute of Pathology, Division of OncogenomicsUniversity of RegensburgRegensburgGermany

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