Transcriptomics

Dataset Information

4

Gene expression profiling of sequential metastatic biopsies for biomarker discovery in breast cancer


ABSTRACT: The feasibility of longitudinal metastatic biopsies for gene expression profiling in breast cancer is unexplored. Dynamic changes in gene expression can potentially predict efficacy of targeted cancer drugs. Patients enrolled in a phase III trial of metastatic breast cancer with sunitinib combined with docetaxel (SU+DOC) versus docetaxel alone (DOC) were offered to participate in a translational substudy comprising longitudinal fine needle aspiration biopsies (FNAB) and positron emission imaging before (T1) and two weeks after start of treatment (T2). Aspirated tumor material was used for microarray analysis, and treatment-induced changes (T2 versus T1) in gene expression and standardized uptake values were investigated. Twenty-one patients were included in the docetaxel ± sunitinib trial at Karolinska and 18 of them agreed to participate in the substudy. Of the 18 women enrolled, 8 were randomly assigned to SU+DOC and 10 to DOC. Metastatic FNAB were carried out in 17 of the 18 patients at both time points with no complications reported. Representative tumor material, sufficient for RNA extraction was obtained in 15 patients at T1 and 14 patients at T2. Matched samples both at T1 and T2 were obtained for 14 subjects, 7 in each arm. The main objective was to determine whether gene expression profiling is feasible using sequential, intra-patient FNAB. Secondary objectives were to identify potential biomarkers of early response by gene expression and/or functional imaging and to explore drug action in vivo by changes in gene expression. A Karolinska substudy of the docetaxel ± sunitinib phase III clinical trial utilising sequential metastatic fine needle aspiration biopsies (FNAB) and 18-F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT). In brief, the randomized docetaxel ± sunitinib trial compared sunitinib combined with docetaxel (SU+DOC) versus docetaxel alone (DOC), as first line therapy in patients with HER2 negative metastatic breast cancer. Patients in the exploratory substudy were subjected to baseline FDG PET/CT assessment, followed by FNAB of one tumor lesion prior to start of treatment (Time point T1). FDG PET/CT and FNAB were repeated at Day 14 ± 1 (Time point T2) when sunitinib has achieved steady state.

ORGANISM(S): Homo sapiens  

SUBMITTER: Hans Jacobsson   Linda S Lindström  Theodoros Foukakis  Elham Hedayati  Hanjing Xie  Patricia Sandqvist  John Lövrot  Carla Giorgetti  Jonas Bergh 

PROVIDER: E-GEOD-54323 | ArrayExpress | 2015-04-14

SECONDARY ACCESSION(S): GSE54323PRJNA236335

REPOSITORIES: GEO, ArrayExpress

Similar Datasets

| GSE54323 | GEO
| GSE58837 | GEO
2012-12-01 | E-MEXP-3730 | ArrayExpress
2011-11-01 | GSE21217 | GEO
2011-11-01 | E-GEOD-21217 | ArrayExpress
| GSE99790 | GEO
| GSE110685 | GEO
| GSE7116 | GEO
2013-01-17 | E-MTAB-1049 | ArrayExpress
2017-01-03 | PXD001888 | Pride