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

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Tumor Biology

Abstract

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.

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Authors and Affiliations

  1. Haematology and Oncology Outpatient Cancer Care Center, Franz-Schrank-Str. 2, 80638, Munich, Germany

    Oliver J. Stoetzer & Christoph Salat

  2. Institute of Clinical Chemistry, University Hospital Munich, Marchioninistr. 15, 81366, Munich, Germany

    Debora M. I. Fersching, Barbara Siegele, Dorothea Nagel & Stefan Holdenrieder

  3. Breast Cancer Center Klinikum Dritter Orden, Menzinger Str. 44, 80638, Munich, Germany

    Oliver Steinkohl & Christian J Gabka

  4. Red Cross Breast Cancer Center II, Taxisstr. 3, 80637, Munich, Germany

    Ulrich Hamann & Michael Braun

  5. Breast Cancer Center Dr. Geisenhofer, Hirschauer Str. 6, 80538, Munich, Germany

    Axel-Mario Feller

  6. Medical Clinic III, University Hospital Munich, Marchioninistr. 15, 81366, Munich, Germany

    Volker Heinemann

  7. Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Sigmund-Freud Str. 25, 53105, Bonn, Germany

    Stefan Holdenrieder

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  1. Oliver J. Stoetzer
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Correspondence to Stefan Holdenrieder.

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Stoetzer, O.J., Fersching, D.M.I., Salat, C. et al. Circulating immunogenic cell death biomarkers HMGB1 and RAGE in breast cancer patients during neoadjuvant chemotherapy. Tumor Biol. 34, 81–90 (2013). https://doi.org/10.1007/s13277-012-0513-1

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  • DOI: https://doi.org/10.1007/s13277-012-0513-1

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