Transcriptomics

Dataset Information

627

Transcription profiling by array of human breast cancers after treatment with tamoxifen


ABSTRACT: 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.

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens  

SUBMITTER: Benjamin Haibe-Kains  

PROVIDER: E-GEOD-6532 | ArrayExpress | 2008-06-20

SECONDARY ACCESSION(S): GSE6532PRJNA98807

REPOSITORIES: GEO, ArrayExpress

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Publications

Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade.

Loi Sherene S   Haibe-Kains Benjamin B   Desmedt Christine C   Lallemand Françoise F   Tutt Andrew M AM   Gillet Cheryl C   Ellis Paul P   Harris Adrian A   Bergh Jonas J   Foekens John A JA   Klijn Jan G M JG   Larsimont Denis D   Buyse Marc M   Bontempi Gianluca G   Delorenzi Mauro M   Piccart Martine J MJ   Sotiriou Christos C  

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20070401 10


PURPOSE: A number of microarray studies have reported distinct molecular profiles of breast cancers (BC), such as 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. Therefore, refinement of their molecular definition is needed. MATERIALS AND METHODS: We have previously  ...[more]

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