Prediction of response to neoadjuvant chemotherapy in breast cancer patients by circulating apoptotic biomarkers nucleosomes, DNAse, cytokeratin-18 fragments and survivin

• Circulating nucleosomes and survivin are elevated in sera of patients with locally confined and metastatic breast cancer.
• Cytokeratin-18 fragments (M30-antigen) and breast tumor markers CEA and CA 15-3 are only elevated in metastatic disease.
• High pretherapeutic nucleosome levels indicate poor response to neoadjuvant chemotherapy.
• Apoptotic biomarkers bear valuable information for diagnosis and therapy response in breast cancer patients.

Biomarkers predicting response to neoadjuvant chemotherapy in locally confined breast cancer (LBC) are highly needed. We prospectively assessed serial blood levels of apoptotic biomarkers nucleosomes, DNAse activity, cytokeratin-18 fragments (M30) and survivin in 51 LBC patients and correlated them with response to neoadjuvant treatment and established tumor markers. As controls, we used 31 healthy subjects, 13 patients with benign diseases and 28 with metastatic breast cancer (MBC). Levels of nucleosomes and survivin were elevated in LBC and MBC while M30, CEA and CA 15-3 levels were only elevated in MBC. During neoadjuvant chemotherapy, LBC patients with no change of disease (N = 13) had significantly higher pretherapeutic levels of nucleosomes than patients with remission (N = 38). We conclude that apoptotic biomarkers bear valuable information for diagnosis and therapy response prediction in LBC patients.