Breast Cancer Research and Treatment

, Volume 124, Issue 2, pp 403–412

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

Authors

    • Department of Gynecology and ObstetricsUniversity of Tübingen
  • Volkmar Müller
    • Department of GynecologyUniversity Medical Center Hamburg-Eppendorf
  • Bahriye Aktas
    • Department of Gynecology and ObstetricsUniversity Hospital of Essen
  • Wolfgang Janni
    • Department of Gynecology and ObstetricsUniversity of Düsseldorf
  • Andreas Schneeweiss
    • Department of Gynecology and ObstetricsUniversity of Heidelberg
  • Elmar Stickeler
    • Department of Gynecology and ObstetricsUniversity of Freiburg
  • Claus Lattrich
    • Department of Gynecology and ObstetricsUniversity of Regensburg
  • Christian R. Löhberg
    • Department of Gynecology and ObstetricsUniversity of Erlangen
  • Erich Solomayer
    • Department of Gynecology and ObstetricsUniversity of Homburg
  • Brigitte Rack
    • Department of Gynecology and ObstetricsUniversity of Munich
  • Sabine Riethdorf
    • Institute of Tumor BiologyUniversity Medical Center Hamburg-Eppendorf
  • Christoph Klein
    • Institute of Pathology, Division of OncogenomicsUniversity of Regensburg
  • Christian Schindlbeck
    • Department of Gynecology and ObstetricsUniversity of Munich
  • Kerstin Brocker
    • Department of Gynecology and ObstetricsUniversity of Heidelberg
  • Sabine Kasimir-Bauer
    • Department of Gynecology and ObstetricsUniversity Hospital of Essen
  • Diethelm Wallwiener
    • Department of Gynecology and ObstetricsUniversity of Tübingen
  • Klaus Pantel
    • Institute of Tumor BiologyUniversity Medical Center Hamburg-Eppendorf
Clinical trial

DOI: 10.1007/s10549-010-1163-x

Cite this article as:
Fehm, T., Müller, V., Aktas, B. et al. Breast Cancer Res Treat (2010) 124: 403. doi:10.1007/s10549-010-1163-x

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.

Keywords

Breast cancerCirculating tumor cellsHER2Metastasis

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

Copyright information

© Springer Science+Business Media, LLC. 2010