Project description:Triple-negative breast cancer (TNBC) is considered the most aggressive type of breast cancer with limited options for therapy. TNBC is a heterogeneous disease and tumours has been classified into TNBC subtypes using gene expression profiling to distinguish basal-like1 (BL1), basal-like2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal/stem-like (MSL), luminal androgen receptor (LAR) and one non-classifiable group (called unstable, UNS). The aim of this study was to verify the clinical relevance of molecular subtyping of TNBCs by expression analysis to improve the individual indication of systemic therapy.
Project description:Triple negative breast cancers lack targeted therapies with little side effects and contain higher percentage of cancer stem cells than the other breast cancer subtypes. Genes capturing the features of cancer stem cells of such diseases may serve as potential subtyping marker or therapeutic targets for triple negative breast cancer management. This data descriptor presents a set of transcriptome data from 3 cohorts of cancer stem cells as represented as CD44+/CD24-/low and 2 cohorts of non-cancer stem cells isolated from triple negative breast cancer cells, each having 3 replicates.
Project description:Triple-negative (TN) breast cancers need to be refined in order to identify therapeutic subgroups of patients. We conducted an unsupervised analysis of microarray gene-expression profiles of 107 TN breast cancer patients and undertook robust functional annotation of the molecular entities found by means of numerous approaches including immunohistochemistry and gene-expression signatures. An 87 TN external cohort was used for validation. Fuzzy clustering separated TN 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 (EFS) (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). EFS analysis results were confirmed when our cohort was pooled with external cohort (n = 194; P = 0.01). Functional annotation showed that 22% of TN patients were not basal-like (C1). C1 was enriched in luminal subtypes and positive androgen receptor (luminal androgen receptor [LAR]). 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 (HIR) and low M2-like macrophages were a hallmark of C3, and that these patients had a better EFS than C2 patients, characterized by low immune response (LIR) and high M2-like macrophages: P = 0.02 for our cohort, and P = 0.03 for pooled cohorts. We identified 3 subtypes of TN patients: LAR (22%), basal-like with LIR and high M2-like macrophages (45%) and basal-enriched with HIR and low M2-like macrophages (33%). We pointed out that macrophages and other immune effectors offer a variety of therapeutic targets in breast cancer, and particularly in TN basal-like tumours. Furthermore, we showed that CK5 antibody was better suited than CK5/6 antibody to subtype TN patients. Subtyping molecular characterization within a cohort of 107 TN-IHC by means of gene expression profiling
Project description:This study developed a triple-negative breast cancer (TNBC) surrogate subtype classification that represents TNBC subtypes based on the Vanderbilt subtype classification The web-based subtyping tool TNBCtype was used to classify the TNBC cohort into Vanderbilt subtypes
Project description:Triple negative breast cancer is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents. The purpose of this study was to explore the clinical relevance of Lehmann triple negative breast cancer subtypes by identifying any differences in response to neoadjuvant chemotherapy among them.
Project description:Triple negative breast tumours from archived formalin fixed paraffin embeded samples of the National Cancer Institute of Mexico were analyzed for differential gene expressión.
