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Monitoring serum HER2 levels during neoadjuvant trastuzumab treatment within the GeparQuattro trial

Breast Cancer Research and Treatment volume 123, pages 437–445 (2010)Cite this article

Abstract

In the context of neoadjuvant therapy (NT) for breast cancer patients, different targeted therapy approaches are currently evaluated in clinical trials. Serum markers could help to monitor and optimize such treatment strategies. We investigated human epidermal growth factor receptor 2 serum (sHER2) levels in 175 breast cancer patients participating in the GeparQuattro trial. This study incorporated NT approaches and additional trastuzumab treatment for all patients with HER2-positive tumors. Human epidermal growth factor receptor 2 serum levels were measured by enzyme-linked immunosorbent assay (ELISA) before initiation of NT and after NT (pre-surgery) in a HER2-positive (n = 90) and a HER2-negative patient cohort (n = 85). Median pre-chemotherapy sHER2 levels were higher in patients with positive HER2 status of the primary tumor than in patients with negative HER2 status (14.9 ng/ml vs. 7.7 ng/ml, P < 0.001). A pre-chemotherapy sHER2 cut-off level of 10 ng/ml had the best sensitivity and specificity in discriminating between HER2-positive and HER2-negative primary tumors. In HER2-positive patients, we found a significant positive association between pathological complete remission (pCR) and elevated sHER2 levels (above 15 ng/ml, P = 0.045) and a decrease of sHER2 levels during NT (P = 0.02), which was also significant in multivariate analysis (OR = 3.29, 95% CI 1.001–10.89, P = 0.049). In HER2-negative patients, we observed no association between sHER2 levels and pCR (P > 0.05). Monitoring sHER2 levels in the presence of anti-HER2 treatment might be an adjunct to the clinical evaluation during NT.

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Acknowledgments

We thank Sylke Krenkel for excellent technical assistance, and the staff of the German Breast Group for support of this translational research project. Most of all, we thank the patients of the clinical trial GeparQuattro who participated in this substudy. Research funding: Christoph Mundhenke, Novartis Oncology; Volkmar Müller, Roche and Siemens Diagnostics

Conflict of interest statement

Advisory role/relationship: Sibylle Loibl, Roche; Jens Huober, Roche; Claus Hanusch, Sanofi Aventis; Hans Tesch, Roche; Volkmar Müller, Roche. Honoraria: Sibylle Loibl, Roche; Gunter von Minckwitz, Roche; Claus Hanusch, Sanofi Aventis; Hans Tesch, Roche; Volkmar Müller, Roche. All other authors have declared no conflict of interest.

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Authors and Affiliations

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

    Isabell Witzel & Volkmar Müller

  2. Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Christine zu Eulenburg

  3. German Breast Group, Forschungs GmbH, Neu Isenburg, Germany

    Sibylle Loibl, Gunter von Minckwitz & Marc Roller

  4. Department of Gynecology and Obstetrics, University Medical Center Kiel, Kiel, Germany

    Christoph Mundhenke

  5. Department of Gynecology, University of Tübingen, Tübingen, Germany

    Jens Huober

  6. Department of Gynecology and Obstetrics, Rotkreuzklinikum München gGmbH, München, Germany

    Claus Hanusch

  7. Johanniter-Krankenhaus, Genthin-Stendal, Stendal, Germany

    Stephan Henschen

  8. Frauenklinik Rheinfelden Betriebs GmbH, Rheinfelden, Germany

    Maik Hauschild

  9. Krankenhaus St. Elisabeth und St. Barbara, Halle, Germany

    Tilmann Lantzsch

  10. Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus, Frankfurt, Germany

    Hans Tesch

  11. Katharinen-Hospital, Unna, Germany

    Kunibert Latos

  12. Onkologische Schwerpunktpraxis, Bielefeld, Germany

    Marianne Just

  13. Frauenklinik der Henriettenstiftung Hannover, Hannover, Germany

    Jörn Hilfrich

  14. Deptartment of Gynecology & Gynecologic Oncology, Dr. Horst Schmidt Klinik, Wiesbaden, Germany

    Jana Barinoff

  15. Department of Gynecology and Obstetrics, HELIOS Hospital Berlin-Buch, Berlin, Germany

    Michael Untch

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  1. Isabell Witzel
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  2. Sibylle Loibl
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  17. Michael Untch
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  18. Volkmar Müller
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Correspondence to Volkmar Müller.

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Supplementary Fig 1: Disposition of patients (CONSORT diagram). (PPT 62 kb)

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Witzel, I., Loibl, S., von Minckwitz, G. et al. Monitoring serum HER2 levels during neoadjuvant trastuzumab treatment within the GeparQuattro trial. Breast Cancer Res Treat 123, 437–445 (2010). https://doi.org/10.1007/s10549-010-1030-9

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  • DOI: https://doi.org/10.1007/s10549-010-1030-9

Keywords

  • Breast cancer
  • Neoadjuvant therapy
  • HER2
  • Serum