Plasma HMGB-1 after the initial dose of epirubicin/docetaxel in cancer

Eur J Clin Invest. 2013 Mar;43(3):286-91. doi: 10.1111/eci.12043. Epub 2013 Jan 25.

Abstract

Background: The response of breast cancer patients to neoadjuvant chemotherapy (NCT) is highly heterogeneous, and reliable predictive instruments remain to be defined. High-mobility group box-1 (HMGB-1) protein is a cell death marker, which is easily detectable in plasma. We hypothesized that the initial dose of NCT with epirubicin/docetaxel induces changes in plasma HMGB-1 which could allow for an early prediction of response to therapy.

Materials and methods: First, we analysed whether epirubicin/docetaxel releases HMGB-1 from HCC1143 breast cancer cells in vitro. Thereafter, plasma HMGB-1 levels before and 1-4 days after the first dose of epirubicin/docetaxel-based NCT were determined in 41 breast cancer patients and correlated with pathological response to treatment.

Results: Treatment of HCC1143 cells with epirubicin/docetaxel resulted in a significant HMGB-1 release in vitro. In vivo, HMGB-1 levels increased significantly only in responders (pathological complete response or partial remission, n = 22) but not in nonresponders (stable or progressive disease, n = 19).

Conclusion: Our data suggest that early dynamic changes of plasma HMGB1 could be a promising biomarker to predict the final response to NCT in breast cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers / metabolism
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Cell Survival / drug effects
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Epirubicin / administration & dosage
  • Female
  • HMGB1 Protein / metabolism*
  • Humans
  • Neoadjuvant Therapy
  • Taxoids / administration & dosage
  • Tumor Cells, Cultured

Substances

  • Biomarkers
  • HMGB1 Protein
  • Taxoids
  • Docetaxel
  • Epirubicin