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

作者：Pascal Jézéquel, Delphine Loussouarn, Catherine Guérin‐Charbonnel, L. Campion, Antoine Vanier, Wilfried Gouraud, Hamza Lasla, Catherine Guette, Isabelle Valo, Véronique Verrièle, Mario Campone · 发表于：Breast Cancer Research · 年份：2015 · DOI：10.1186/s13058-015-0550-y · 被引用次数：342 · 研究领域：Breast Cancer Treatment Studies、Cancer Immunotherapy and Biomarkers、Breast Lesions and Carcinomas

INTRODUCTION: 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. Dissecti...