Breast Cancer Research and Treatment

, Volume 123, Issue 2, pp 437–445 | Cite as

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

  • Isabell Witzel
  • Sibylle Loibl
  • Gunter von Minckwitz
  • Christoph Mundhenke
  • Jens Huober
  • Claus Hanusch
  • Stephan Henschen
  • Maik Hauschild
  • Tilmann Lantzsch
  • Hans Tesch
  • Kunibert Latos
  • Marianne Just
  • Jörn Hilfrich
  • Jana Barinoff
  • Christine zu Eulenburg
  • Marc Roller
  • Michael Untch
  • Volkmar Müller
Clinical trial

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.

Keywords

Breast cancer Neoadjuvant therapy HER2 Serum 

Supplementary material

10549_2010_1030_MOESM1_ESM.ppt (62 kb)
Supplementary Fig 1: Disposition of patients (CONSORT diagram). (PPT 62 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Isabell Witzel
    • 1
  • Sibylle Loibl
    • 3
  • Gunter von Minckwitz
    • 3
  • Christoph Mundhenke
    • 4
  • Jens Huober
    • 5
  • Claus Hanusch
    • 6
  • Stephan Henschen
    • 7
  • Maik Hauschild
    • 8
  • Tilmann Lantzsch
    • 9
  • Hans Tesch
    • 10
  • Kunibert Latos
    • 11
  • Marianne Just
    • 12
  • Jörn Hilfrich
    • 13
  • Jana Barinoff
    • 14
  • Christine zu Eulenburg
    • 2
  • Marc Roller
    • 3
  • Michael Untch
    • 15
  • Volkmar Müller
    • 1
  1. 1.Department of GynecologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  2. 2.Department of Medical Biometry and EpidemiologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  3. 3.German Breast Group, Forschungs GmbHNeu IsenburgGermany
  4. 4.Department of Gynecology and ObstetricsUniversity Medical Center KielKielGermany
  5. 5.Department of GynecologyUniversity of TübingenTübingenGermany
  6. 6.Department of Gynecology and ObstetricsRotkreuzklinikum München gGmbHMünchenGermany
  7. 7.Johanniter-Krankenhaus, Genthin-StendalStendalGermany
  8. 8.Frauenklinik Rheinfelden Betriebs GmbHRheinfeldenGermany
  9. 9.Krankenhaus St. Elisabeth und St. BarbaraHalleGermany
  10. 10.Onkologische Gemeinschaftspraxis am Bethanien-KrankenhausFrankfurtGermany
  11. 11.Katharinen-HospitalUnnaGermany
  12. 12.Onkologische SchwerpunktpraxisBielefeldGermany
  13. 13.Frauenklinik der Henriettenstiftung HannoverHannoverGermany
  14. 14.Deptartment of Gynecology & Gynecologic OncologyDr. Horst Schmidt KlinikWiesbadenGermany
  15. 15.Department of Gynecology and ObstetricsHELIOS Hospital Berlin-BuchBerlinGermany

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