Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of breast cancer samples to predict response to anthracycline/taxane chemotherapy .

ABSTRACT: EORTC 10994 phase III breast cancer clinical trial comparing FEC (5-fluorouracil, cyclophosphamide, epirubicin) with ET (epirubicin, docetaxel). 161 needle biopsies of locally advanced or large operable breast tumours were hybridised to Affymetrix X3P chips. The array data from the ER negative tumours (28/65 pathological CR in the FEC arm, 27/59 pathological CR in the ET arm) were used to validate the cell line-based chemotherapy response predictors developed by the Potti/Nevins group at Duke University (doi:10.1038/nm1491). Experiment Overall Design: We analyzed 161 arrays of breast carcinoma.

ORGANISM(S): Homo sapiens

SUBMITTER: Pierre Farmer

PROVIDER: E-GEOD-6861 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial.

Bonnefoi Hervé H Potti Anil A Delorenzi Mauro M Mauriac Louis L Campone Mario M Tubiana-Hulin Michèle M Petit Thierry T Rouanet Philippe P Jassem Jacek J Blot Emmanuel E Becette Véronique V Farmer Pierre P André Sylvie S Acharya Chaitanya R CR Mukherjee Sayan S Cameron David D Bergh Jonas J Nevins Joseph R JR Iggo Richard D RD

The Lancet. Oncology 20071119 12

<h4>Background</h4>We have previously described gene-expression signatures that predict growth inhibitory and cytotoxic effects of common chemotherapeutic drugs in vitro. The aim of this study was to confirm the validity of these gene-expression signatures in a large series of patients with oestrogen-receptor-negative breast tumours who were treated in a phase III neoadjuvant clinical trial.<h4>Methods</h4>This trial compares a non-taxane regimen (fluorouracil, epirubicin, and cyclophosphamide [ ...[more]

PMID: 18024211

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Project description:PURPOSE: Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant TOP trial, in which patients with estrogen receptor (ER)-negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase IIα (TOP2A) and to develop a gene expression signature to identify those patients who do not benefit from anthracyclines. METHODS: The TOP trial included 149 patients, of which 141 were evaluable for response prediction analyses. The primary endpoint was pathological complete response (pCR). TOP2A and gene expression profiles were evaluated using pre-epirubicin biopsies. Gene expression data from ER-negative samples of the EORTC 10994/BIG 00-01 and MDACC 2003-0321 neoadjuvant trials were used for validation purposes. RESULTS: A pCR was obtained in 14% of the evaluable TOP patients. TOP2A amplification, but not protein overexpression, was significantly associated with pCR (p=0.001 and 0.22). We developed an “anthracycline-based score (A-Score)” that combines three signatures: a TOP2A gene signature and two previously published signatures related to tumor invasion and immune response. The A-Score was characterized by a high negative predictive value (NPV=0.98 [95% CI: 0.90-1.00]) overall, and in the HER2-negative and HER2-positive subpopulations. Its performance was independently confirmed in the anthracycline-based (FAC/FEC) arms of the two validation trials (BIG 00-01: 0.80 [0.61-0.92] and MDACC 2003-0321: 1.00 [0.80-1.00]). CONCLUSION: Given its high NPV, the A-Score could become, if further validated, a useful clinical tool to identify those patients who do not benefit from anthracyclines and could therefore be spared the non-negligible side effects. Predicting the efficacy of anthracyclines (epirubicin) in breast cancer (BC) patients (TOP trial) 120 microarray experiments from primary ER-negative breast tumors of anthracycline-treated patients. No replicate, no reference sample.

Dataset Information

Transcription profiling of breast cancer samples to predict response to anthracycline/taxane chemotherapy .

Publications

Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial.

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