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Levels of ALU 115, ALU 247, DNA integrity ([1, 2]) and of the tumour markers CA 15-3 and CEA were analysed in the blood of 152 patients. Plasma levels of ALU 115 and ALU 247 were significantly higher in patients with locally confined (LBC; N = 65), metastatic breast cancer (MBC; N = 47), and benign diseases (N = 12) than in healthy controls (p < 0.001 for all comparisons). DNA integrity, CEA, and CA 15-3 were significantly higher in MBC than in benign controls and LBC but could not identify LBCs. The best discrimination of LBC from healthy controls was achieved by ALU 115 and ALU 247 (AUC 95.4 and 95.5 %) and of MBC from all control groups by CA 15-3 and CEA (AUC 83.2 and 79.1 %). Plasma DNA is valuable for the detection of LBC, while established tumour markers are most informative in MBC.

In comparison with healthy controls, cancer patients demonstrated elevated serum levels of nucleosomes and HMGB1 while sRAGE levels were decreased. During locoregional and systemic cytotoxic therapies, a high release of nucleosomes and HMGB1 as well as low release of sRAGE before and during the initial phase of the treatment was found to be associated with poor response to the therapy and patient survival. Therefore, immunogenic cell death markers are promising tools for the prognosis, therapy prediction and monitoring in cancer patients.

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e21067 Background: In breast cancer patients undergoing neoadjuvant chemotherapy before surgery, biomarkers for predicting the response to the therapy are highly needed. Methods: Concentrations of ALU115, ALU247 and DNA integrity were analyzed in prospectively collected plasma of 68 patients with localized breast cancer (UICC II and III), of 47 patients with metastatic breast cancer and 28 healthy women as controls. In all 68 patients with breast cancer who had completed the course of chemotherapy until surgery, DNA and tumor biomarkers CEA and CA 15-3 were evaluated concerning response to therapy (no change, NC: N=18; partial remission, PR: N=35; complete remission, CR: 15). Results: Plasma levels of ALU 115 and ALU 247 were significantly higher in patients with localized (medians 16.3 and 16.8 ng/mL) and metastasized breast cancer (22.2 and 29.8 ng/mL) than in healthy controls (1.8 and 1.9 ng/mL). However, plasma DNA integrity showed no significant differences between the diagnostic groups. AUCs in ROC curves for discrimination of localized breast cancer from healthy controls were 96% for ALU 115 and ALU 247, respectively, and 60% for DNA integrity. Concerning therapy response, pretherapeutic ALU 115, 247, and DNA integrity and also CEA and CA 15-3 were not significantly different when patients with and without remission (CR vs PR+NC and CR+PR vs NC) were compared. Conclusions: While plasma DNA levels are valuable for discrimination of breast cancer patients from controls, pretherapeutic DNA integrity provides no additive diagnostic information nor indicates response to neoadjuvant therapy.