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

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Abstract

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.

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Abbreviations

CK:

Cytokeratin

CTC:

Circulating tumor cell

DAPI:

4′,6-diamidino-2-phenylindole.

FDA:

Food and drug administration

HER2:

Human epidermal growth factor receptor 2

EpCam:

Epithelial cell adhesion molecule

ER:

Estrogen receptor

FISH:

Fluorescence in situ hybridization

FITC:

Fluorescein isothiocyanate

IHC:

Immunohistochemistry

MUC1:

Mucin 1

N/A:

Not available

PR:

Progesterone receptor

RT-PCR:

Reverse transcriptase polymerase chain reaction

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Acknowledgements

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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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, University of Tübingen, Calwer Strasse 7, 72076, Tübingen, Germany

    Tanja Fehm & Diethelm Wallwiener

  2. Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Volkmar Müller

  3. Department of Gynecology and Obstetrics, University Hospital of Essen, Hufelandstrasse 55, 45147, Essen, Germany

    Bahriye Aktas & Sabine Kasimir-Bauer

  4. Department of Gynecology and Obstetrics, University of Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany

    Wolfgang Janni

  5. Department of Gynecology and Obstetrics, University of Heidelberg, Vossstrasse 9, 69115, Heidelberg, Germany

    Andreas Schneeweiss & Kerstin Brocker

  6. Department of Gynecology and Obstetrics, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany

    Elmar Stickeler

  7. Department of Gynecology and Obstetrics, University of Regensburg, Caritas Krankenhaus St. Josef, Landshuter Strasse 65, 93053, Regensburg, Germany

    Claus Lattrich

  8. Department of Gynecology and Obstetrics, University of Erlangen, Universitaetsstrasse 21-23, 91054, Erlangen, Germany

    Christian R. Löhberg

  9. Department of Gynecology and Obstetrics, University of Homburg, Kirrberger Strasse 100, 66424, Homburg/Saar, Germany

    Erich Solomayer

  10. Department of Gynecology and Obstetrics, University of Munich, Maistrasse 11, 80337, München, Germany

    Brigitte Rack & Christian Schindlbeck

  11. Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Sabine Riethdorf & Klaus Pantel

  12. Institute of Pathology, Division of Oncogenomics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany

    Christoph Klein

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  1. Tanja Fehm
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  2. Volkmar Müller
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  3. Bahriye Aktas
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Corresponding author

Correspondence to Tanja Fehm.

Additional information

This study is conducted on behalf of the DETECT Study Group.

T. Fehm and V. Müller contributed equally to this work.

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Fehm, T., Müller, V., Aktas, B. et al. HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat 124, 403–412 (2010). https://doi.org/10.1007/s10549-010-1163-x

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