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Triple-negative breast cancers need to be refined in order to identify therapeutic subgroups of patients.    Methods  We conducted an unsupervised analysis of microarray gene-expression profiles of 107 triple-negative breast cancer patients and undertook robust functional annotation of the molecular entities found by means of numerous approaches including immunohistochemistry and gene-expression signatures. A triple-negative external cohort ( n  = 87) was used for validation.    Results  Fuzzy clustering separated triple-negative tumours into three clusters: C1 (22.4%), C2 (44.9%) and C3 (32.7%). C1 patients were older (mean = 64.6 years) than C2 (mean = 56.8 years;  P  = 0.03) and C3 patients (mean = 51.9 years;  P  = 0.0004). Histological grade and Nottingham prognostic index were higher in C2 and C3 than in C1 ( P  < 0.0001 for both comparisons). Significant event-free survival ( P  = 0.03) was found according to cluster membership: patients belonging to C3 had a better outcome than patients in C1 ( P  = 0.01) and C2 ( P  = 0.02). Event-free survival analysis results were confirmed when our cohort was pooled with the external cohort ( n  = 194;  P  = 0.01). Functional annotation showed that 22% of triple-negative patients were not basal-like (C1). C1 was enriched in luminal subtypes and positive androgen receptor (luminal androgen receptor). C2 could be considered as an almost pure basal-like cluster. C3, enriched in basal-like subtypes but to a lesser extent, included 26% of claudin-low subtypes. Dissection of immune response showed that high immune response and low M2-like macrophages were a hallmark of C3, and that these patients had a better event-free survival than C2 patients, characterized by low immune response and high M2-like macrophages:  P  = 0.02 for our cohort, and  P  = 0.03 for pooled cohorts.    Conclusions  We identified three subtypes of triple-negative patients: luminal androgen receptor (22%), basal-like with low immune response and high M2-like macrophages (45%), and basal-enriched with high immune response and low M2-like macrophages (33%). We noted out that macrophages and other immune effectors offer a variety of therapeutic targets in breast cancer, and particularly in triple-negative basal-like tumours. Furthermore, we showed that CK5 antibody was better suited than CK5/6 antibody to subtype triple-negative patients.    Electronic supplementary material  The online version of this article (doi:10.1186/s13058-015-0550-y) contains supplementary material, which is available to authorized users.

Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response