E-GEOD-6532 - Transcription profiling by array of human breast cancers after treatment with tamoxifen

Released on 20 June 2008, last updated on 30 April 2012
Homo sapiens
Samples (741)
Arrays (3)
Protocols (5)
Purpose: A number of microarray studies have reported distinct molecular profiles of breast cancers (BC): basal-like, ErbB2-like and two to three luminal-like subtypes. These were associated with different clinical outcomes. However, although the basal and the ErbB2 subtypes are repeatedly recognized, identification of estrogen receptor (ER)-positive subtypes has been inconsistent. Refinement of their molecular definition is therefore needed. Materials and methods: We have previously reported a gene-expression grade index (GGI) which defines histological grade based on gene expression profiles. Using this algorithm, we assigned ER-positive BC to either high or low genomic grade subgroups and compared these to previously reported ER-positive molecular classifications. As further validation, we classified 666 ER-positive samples into subtypes and assessed their clinical outcome. Results: Two ER-positive molecular subgroups (high and low genomic grade) could be defined using the GGI. Despite tracking a single biological pathway, these were highly comparable to the previously described luminal A and B classification and significantly correlated to the risk groups produced using the 21-gene recurrence score. The two subtypes were associated with statistically distinct clinical outcome in both systemically untreated and tamoxifen-treated populations. Conclusions: The use of genomic grade can identify two clinically distinct ER-positive molecular subtypes in a simple and highly reproducible manner across multiple datasets. This study emphasizes the important role of proliferation-related genes in predicting prognosis in ER-positive BC. Experiment Overall Design: dataset of microarray experiments from primary breast tumors used to assess the reationship between GGI, molecular subtypes, and tamoxifen resistance. Experiment Overall Design: No replicate, no reference sample.
Experiment types
transcription profiling by array, clinical history, co-expression, disease state
Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. Sherene Loi, Benjamin Haibe-Kains, Christine Desmedt, Francoise Lallemand, Andrew M Tutt, Cheryl Gillet, Paul Ellis, Adrian Harris, Jonas Bergh, John A Foekens, Jan G M Klijn, Denis Larsimont, Marc Buyse, Gianluca Bontempi, Mauro Delorenzi, Martine J Piccart, Christos Sotiriou. , Europe PMC 17401012
Investigation descriptionE-GEOD-6532.idf.txt
Sample and data relationshipE-GEOD-6532.sdrf.txt
Raw data (20)Click to browse raw data
Processed data (1)E-GEOD-6532.processed.1.zip
Additional data (20)Click to browse additional data
Array designsA-AFFY-33.adf.txt, A-AFFY-34.adf.txt, A-AFFY-44.adf.txt