Prediction of breast cancer pathological complete response to anthracycline/taxane chemotherapy.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE6861 | GEO | 2007/11/23
SECONDARY ACCESSION(S): PRJNA99107
REPOSITORIES: GEO
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Project description: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.
2008-06-15 | E-GEOD-6861 | biostudies-arrayexpress
Project description:The goal of the study was to identify a gene expression signature capable of predicting a pathological complete response following neoadjuvant anthracycline-based chemotherapy of breast cancer. The samples were taken from the FEC arm (5-fluorouracil, epirubicin, cyclophosphamide) of the EORTC 10994 trial. EORTC 10994 is a phase III clinical trial comparing FEC with ET (epirubicin, docetaxel) in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 200 ng total RNA per chip was amplified using the Affymetrix small sample protocol (IVT then Enzo). 102 tumours were tested on Affymetrix X3P chips. Single biopsies were tested per tumour. The CEL files were quantile normalised using rma. The clinical response measure was pathological complete response (pCR, disappearance of the tumour after chemotherapy with at most scattered invasive cells detected by histology). 102 tumors
2008-12-19 | E-GEOD-4779 | biostudies-arrayexpress
Project description:The goal of the study was to identify a gene expression signature capable of predicting a pathological complete response following neoadjuvant anthracycline-based chemotherapy of breast cancer. The samples were taken from the FEC arm (5-fluorouracil, epirubicin, cyclophosphamide) of the EORTC 10994 trial. EORTC 10994 is a phase III clinical trial comparing FEC with ET (epirubicin, docetaxel) in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 200 ng total RNA per chip was amplified using the Affymetrix small sample protocol (IVT then Enzo). 102 tumours were tested on Affymetrix X3P chips. Single biopsies were tested per tumour. The CEL files were quantile normalised using rma. The clinical response measure was pathological complete response (pCR, disappearance of the tumour after chemotherapy with at most scattered invasive cells detected by histology).
2008-12-19 | GSE4779 | GEO
Project description:EORTC 10994 is a phase III clinical trial comparing FEC with ET in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 100 ng total RNA per chip were amplified using the Affymetrix small sample protocol (IVT then Enzo). 49 tumours were tested on Affymetrix U133A chips. The CEL files were quantile normalised together using rma. Clinical response data are not available yet. See doi:10.1038/sj.onc.1208561 Farmer et al "Identification of molecular apocrine breast tumours by microarray analysis
2007-08-14 | E-GEOD-1561 | biostudies-arrayexpress
Project description:EORTC 10994 is a phase III clinical trial comparing FEC with ET in patients with large operable, locally advanced or inflammatory breast cancer (www.eortc.be). Frozen biopsies were taken at randomisation. RNA was extracted from 100um thickness of 14G core needle biopsies. Adjacent sections were tested by H&E to confirm >20% tumour cell content. 100 ng total RNA per chip were amplified using the Affymetrix small sample protocol (IVT then Enzo). 49 tumours were tested on Affymetrix U133A chips. The CEL files were quantile normalised together using rma. Clinical response data are not available yet. Keywords = Apocrine carcinoma Keywords = breast cancer
2005-06-01 | GSE1561 | GEO
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.
2010-01-26 | E-GEOD-16446 | biostudies-arrayexpress
Project description:Prospective, non-comparative Phase II multicenter trial (EXPRESSION EudraCT: 2008-006381-29) where the patients received three 3-week cycles of docetaxel (100 mg/m2) followed by three 3-week cycles of 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2) (FEC). The primary end point was the identification of a gene expression signature predictive of pathological complete response (pCR). In this trial, pCR was defined as absence of invasive or non-invasive cancer in the breast. External validation of the predictive performance was performed using publicly available data.
2020-11-15 | GSE140494 | GEO
Project description:The purpose of the present study was to investigate the association of glutathione S-transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n = 123, stage II-III) treated with neoadjuvant P-FEC were analyzed. Tumor samples were obtained by vacuum-assisted core biopsy before P-FEC. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1-negative tumors (80.0%) than GSTP1-positive tumors (30.6%) (P = 0.009) among estrogen receptor (ER)-negative tumors but not among ER-positive tumors (P = 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P = 0.013) among ER-negative tumors. Luminal A, luminal B and HER2-enriched tumors showed a significantly lower GSTP1 positivity than basal-like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER2-enriched tumors showed a higher GSTP1 MI than basal-like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP1 expression can predict pathological response to P-FEC in ER-negative tumors but not in ER-positive tumors. Additionally, GSTP1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER2-enriched tumors than basal-like tumors. Fresh frozen tumor samples obtained by vacuum-assisted core biopsy from one hundred and fifteen patients were subjected to RNA extraction and hybridization on Affymetrix microarrays.
2012-03-20 | E-GEOD-32646 | biostudies-arrayexpress
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.
2010-01-26 | GSE16446 | GEO
Project description:Tumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC) followed by four cycles of docetaxel/capecitabine (TX) on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H).
2012-12-11 | GSE42822 | GEO