Background: In HER2+ patients treated with HER2-targeted monoclonal antibodies in the NeoSphere trial, multivariate analysis showed a complex interplay between immune system and response (Gianni L SABCS 2012). High STAT1 and IGG metagens were associated with pCR, whereas high MHC1 and Interferon-inducible (IF.I) metagenes were associated with resistance. We sought to assess in TN tumors if there is a similar relationship between immune system and response to anthracyclines, which leads to immunogenic cell death Methods: We selected Affymetrix GEPs for 87 TN breast cancers (BCs) treated with neoadjuvant epirubicin monotherapy in the TOP trial (Desmedt C JCO 2011). Association between four previously define immune metagenes (IGG, STAT1, IF.I and MHC1), pCR and distant metastasis free survival (DMFS) were assessed. We assessed in 51 BC cell lines (25 TN) if isolated cells themselves also express those immune-related genes. Results: In TOP trial, immune metagenes were not associated with pCR in univariate analysis. In multivariate analysis, high STAT1 (OR 5.17 (1.66-16.1); p = 0.004) and low MHC1 (OR 0.19 (0.07-0.51); p = 0.001) were associated with pCR. Significance was retained when clinical variables and TOP2A amplification/deletion were included. In univariate analysis for DMFS, only high STAT1 was associated with lower risk of relapse (HR 0.62 (0.43-0.90); p = 0.012). In multivariate, high STAT1 (HR 0.26 (0.12-0.59); p = 0.001) and low IF.I (HR 2.75 (1.26-6.00); p = 0.01) were associated with lower risk of recurrence. Results were similar when only patients with residual disease were considered in the analysis. In BC cell lines, expression of MHC1-related genes was very heterogeneous from low to very high. A group of cell lines, TN and HER2+ in particular, expressed also some IF.I/STAT1 related genes. Conclusions: Multivariate analysis is needed to uncover the contribution of immune components to the response and prognosis of TN tumors treated with anthracyclines, which was similar to the involvement with response of HER2+ tumors to monoclonals. Interferon signaling, defined by STAT1 and IF.I metagenes, and MHC1 expression are related to both the immune system status and tumor cells.