Transcriptomics

Dataset Information

6

TBCRC 001: Randomized Phase II Study of Cetuximab in Combination with Carboplatin in Stage IV Triple Negative Breast Cancer


ABSTRACT: Abstract Background. Epidermal growth factor receptor (EGFR) is a targetable molecule in basal-like breast cancer, which comprises most “triple negative” breast cancer (TNBC), the only breast cancer subtype without established targeted therapy. Methods. In this randomized phase II trial, metastatic TNBC patients received the anti-EGFR antibody cetuximab (250mg/kg/week iv) with carboplatin (AUC2/wk iv) added on progression, or concomitant cetuximab + carboplatin. Molecular subtyping was done on archival specimens and those with accessible tumors provided fresh tissue, before and after 7-14 days of therapy, for microarray analyses to explore EGFR pathway inhibition. Results. Of 102 TNBC patients 74% were of the basal-like molecular subtype. Response rate to cetuximab was 6% (2/31), and was 16% (4/25) to cetuximab + carboplatin after progression. Upfront cetuximab + carboplatin produced responses in 17% (12/71); 31% responded or had prolonged disease stabilization. Time to progression was 2.1 months (95% CI 1.8-5.5) and overall survival 10.4 months (95% CI 7.7-13.1) for those treated with the combination regimen. Among 16 patients with evaluable serial biopsies, genomic patterns of the EGFR pathway showed activated status in 13 and inhibition by therapy in 5. Conclusions. While most TNBC were basal-like, a significant proportion were different subtypes. The aggressive nature of metastatic TNBC leads to limited survival. Despite a promising preclinical rationale and evidence of EGFR pathway activation in most, targeted treatment with cetuximab as a single agent had marginal activity and cetuximab added to carboplatin demonstrated modest activity. Serial biopsies as part of metastatic breast cancer studies are feasible, and this study confirmed that the EGFR pathway was inhibited by therapy in only a minority suggesting ligand-independent activation in most tumors. Tissue acquisition and drug selection based upon individualized pathway activation status should be an important part of future studies of TNBC. This series contains 36 microarrays that are from 18 patients with fresh frozen tissue available from the metastatic site. Pretreatment samples (Bx0) are available for two patients. Pretreatment and post single agent treatment (7-14 days after start of treatment with cetuximab; BxSingle) are available for three patients. Pretreatment and post combination treatment (7-14 days after start of treatment with cetuximab plus carboplatin; BxCombo) are available for eight patients. Two patients have a pretreatment sample, a sample after 7-14 days of treatment with single agent cetuximab, and a third sample 7-14 days on cetuximab plus carboplatin after switching to the combination arm upon progression on the single agent arm. Samples were hybridized with Stratagene common reference spiked with RNA from two breast cancer cell lines (ME16C and MCF-7) on Custom 1x44K Agilent microarrays. Arrays were scanned on an Axon 4000B scanner and analyzed with GenePix Pro software.

ORGANISM(S): Homo sapiens  

SUBMITTER: Anastasia Ivanova   Cynthia Ma  Charles Perou  Francisco J Esteva  Kelly Marcom  Charles M Perou  Andres Forero  Erica Mayer  Michael Chiu  Hope Rugo  Timothy Hobday  Katherine A Hoadley  Mothaffar Rimawi  AnnaMaria Storniolo  Minetta Liu  Madlyn Ferraro  Antonio C Wolff  Lisa A Carey  Philip S Bernard  Eric P Winer  Emily Burrows 

PROVIDER: E-GEOD-23428 | ArrayExpress | 2012-07-13

SECONDARY ACCESSION(S): GSE23428PRJNA131093

REPOSITORIES: GEO, ArrayExpress

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Publications

TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer.

Carey Lisa A LA   Rugo Hope S HS   Marcom P Kelly PK   Mayer Erica L EL   Esteva Francisco J FJ   Ma Cynthia X CX   Liu Minetta C MC   Storniolo Anna Maria AM   Rimawi Mothaffar F MF   Forero-Torres Andres A   Wolff Antonio C AC   Hobday Timothy J TJ   Ivanova Anastasia A   Chiu Wing-Keung WK   Ferraro Madlyn M   Burrows Emily E   Bernard Philip S PS   Hoadley Katherine A KA   Perou Charles M CM   Winer Eric P EP  

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20120604 21


Epidermal growth factor receptor (EGFR) is a targetable receptor frequently overexpressed in basal-like breast cancer, which comprises most triple-negative breast cancers (TNBCs), the only subtype without established targeted therapy.In this randomized phase II trial, patients with metastatic TNBC received anti-EGFR antibody cetuximab (400 mg/m(2) load then 250 mg/m(2) per week intravenously [IV]) alone, with carboplatin (area under the curve of 2, once per week IV) added after progression or as  ...[more]

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