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

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. 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. 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). 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.