Tumor Biology

, Volume 34, Issue 1, pp 81–90 | Cite as

Circulating immunogenic cell death biomarkers HMGB1 and RAGE in breast cancer patients during neoadjuvant chemotherapy

  • Oliver J. Stoetzer
  • Debora M. I. Fersching
  • Christoph Salat
  • Oliver Steinkohl
  • Christian J Gabka
  • Ulrich Hamann
  • Michael Braun
  • Axel-Mario Feller
  • Volker Heinemann
  • Barbara Siegele
  • Dorothea Nagel
  • Stefan HoldenriederEmail author
Research Article


Neoadjuvant chemotherapy in breast cancer patients aims at preoperative reduction of tumor volume for better resection results and prognosis. As not all patients respond to neoadjuvant therapy, predictive biomarkers are needed for more efficient individual management. In prospectively collected sera of 51 consecutive locally confined breast cancer (LBC) patients receiving preoperative, neoadjuvant chemotherapy, value level kinetics of soluble high mobility group box 1 (HMGB1), soluble receptor for advanced glycation end products (sRAGE) as well as the established breast cancer biomarkers CA 15–3 and carcinoembryonic antigen (CEA) were investigated and correlated with therapy response objectified by pathological staging at surgery. In addition, biomarkers were measured in sera of 30 healthy controls (HC), 13 patients with benign breast diseases, and 28 metastatic breast cancer (MBC) patients. Pretherapeutic levels of soluble HMGB1 were decreased in MBC, while sRAGE was already decreased in LBC. In contrast, CA 15–3 and CEA were strongly elevated in MBC, but not in LBC. Combination of sRAGE and CA 15–3 enabled best discrimination of LBC from HC (AUC 78.2 %; sens 58 % at 95 % spec), while CA15-3 and CEA discriminated best between MBC and all controls (AUC 90.9 %; sens 70 % at 95 % spec). In LBC patients undergoing neoadjuvant chemotherapy, nine patients achieved complete remission (CR), 29 achieved partial remission (PR), while 13 had no change of disease (NC). NC patients tended to have higher HMGB1 and lower sRAGE levels before therapy onset (p = 0.056 and p = 0.054), while CA 15–3 and CEA did not predict therapeutic outcome. Furthermore, kinetics of HMGB1 during therapy correlated with efficacy of the treatment (p = 0.053). Markers of immunogenic cell death are valuable for the diagnosis of MBC and early estimation of response to neoadjuvant therapy in LBC patients.


Breast cancer Chemotherapy Therapy monitoring Immunogenic cell death Biomarkers HMGB1 RAGE CA 15–3 CEA Serum 

Supplementary material

13277_2012_513_MOESM1_ESM.ppt (504 kb)
ESM 1 (PPT 503 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Oliver J. Stoetzer
    • 1
  • Debora M. I. Fersching
    • 2
  • Christoph Salat
    • 1
  • Oliver Steinkohl
    • 3
  • Christian J Gabka
    • 3
  • Ulrich Hamann
    • 4
  • Michael Braun
    • 4
  • Axel-Mario Feller
    • 5
  • Volker Heinemann
    • 6
  • Barbara Siegele
    • 2
  • Dorothea Nagel
    • 2
  • Stefan Holdenrieder
    • 2
    • 7
    Email author
  1. 1.Haematology and Oncology Outpatient Cancer Care CenterMunichGermany
  2. 2.Institute of Clinical ChemistryUniversity Hospital MunichMunichGermany
  3. 3.Breast Cancer Center Klinikum Dritter OrdenMunichGermany
  4. 4.Red Cross Breast Cancer Center IIMunichGermany
  5. 5.Breast Cancer Center Dr. GeisenhoferMunichGermany
  6. 6.Medical Clinic IIIUniversity Hospital MunichMunichGermany
  7. 7.Institute of Clinical Chemistry and Clinical PharmacologyUniversity Hospital BonnBonnGermany

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