t group mice was diary treated by intra-peritoneal injection of 50 mg/kg of CHR-6494 diluted in a solution of 10% DMSO/20% 2-hydroxypropyl-b-cyclodextrin in two cycles of five consecutive days for 15 days. The treatment group was randomly divided into a short-time response group, defined by tumor weight at the moment of killing of the control group, and a long-time response group, defined by tumor regrowth after treatment. Mice were killed at the end of treatment, and tumors from both groups were excised and weighted. The mean volume of tumor mass was expressed as means.e.m. for each mouse group, and significance was assessed by means of the MannWhitney Utest. Values of Po0.05 were considered statistically significant. Upon killing mice, colon, lung, liver and kidney tissues were obtained to analyze endogenous toxicity by hematoxylin and eosin. Conflict of interest MC, DM, SP, JMcD, JO, DB, DK and SC are employees of Chroma Therapeutics. Acknowledgements The research leading to these results has received funding from the European Community’s Sixth Framework Programme under grant agreement no. LSHG-CT-2006-037415–SMARTER project, grant numbers SAF2007-00027-65134, Consolider CSD2006-49 and Dr. Josef PP 242 Steiner Cancer Research Foundation. ME is an ICREA Research Professor. Accumulating evidence indicates that pre-therapy anticancer immune responses significantly influence disease progression in breast carcinoma patients.1,2 This corollary has also been perceived in the prognosis of other malignancies,3-5 including colorectal carcinomas.6,7 The infiltration of CD8 + lymphocytes in primary breast cancer lesions is positively associated with both overall and relapse-free survival, especially if the tumors lack immunosuppressive CD68 + macrophages.8-10 Similarly, the absence of regulatory T cells in diagnostic breast cancer biopsies has a positive impact on the long-term fate of patients after adjuvant chemotherapy.11,12 A high frequency of infiltrating lymphocytes detected in diagnostic biopsies also 
constitutes an independent predictive biomarker for the induction of pathological complete responses in locally advanced breast cancers.13-16 In the neoadjuvant setting, chemotherapeutic responses have been associated with the de novo induction of local immune responses.From this analysis, we established a series PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19858156 of gene signatures or “metagenes” reflecting correlated gene expression patterns with special reference to the immune response, the ER stress response, autophagy, or lysosomes. We then interrogated correlated the clinical relevance of these metagenes among each other, in several independent cohorts of breast cancers subjected to neo-adjuvant chemotherapy, and evaluated their impact on patient survival post-chemotherapy. Our results reveal the clinical relevance of several immunity-related metagenes, despite the apparently limited impact on local cellular stress responses. Results and Discussion Immune- and stress-related metagenes with a high degree of reproducibility across data sets Among genes known to relate to the immune system, ER-stress, autophagy, or lysosomes, we determined aggregate patterns of coordinately expressed genes by hierarchical clustering and principal component analyses of the initial data set of 522 breast cancer microarrays accessible in The Cancer Genome Atlas. Thresholds were arbitrarily set so that this operation would yield 1820 metagenes in each of the 4 categories. P value of metagene reproducibility. each of