Gene expression profiling of sequential metastatic biopsies for biomarker discovery in breast cancer
| Autor: | Jonas Bergh, Linda S. Lindström, Hans Jacobsson, John Lövrot, Carla Giorgetti, Patricia Sandqvist, Hanjing Xie, Theodoros Foukakis, Elham Hedayati |
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| Rok vydání: | 2014 |
| Předmět: |
Oncology
Adult Cancer Research medicine.medical_specialty Pathology Indoles Combination therapy Biopsy Breast Neoplasms Docetaxel Multimodal Imaging Breast cancer Internal medicine Antineoplastic Combined Chemotherapy Protocols Genetics medicine Biomarkers Tumor Sunitinib Humans Pyrroles Prospective Studies Neoplasm Metastasis Prospective cohort study skin and connective tissue diseases Aged Cell Proliferation medicine.diagnostic_test business.industry Gene Expression Profiling food and beverages General Medicine Middle Aged medicine.disease Metastatic breast cancer Research Papers Cell Hypoxia Gene expression profiling Exact test Positron-Emission Tomography Molecular Medicine Female Taxoids sense organs business Tomography X-Ray Computed medicine.drug |
| Zdroj: | Molecular oncology. 9(7) |
| ISSN: | 1878-0261 |
| Popis: | 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 docetaxel monotherapy versus combination of docetaxel + sunitinib were offered to participate in a translational substudy comprising longitudinal fine needle aspiration biopsies and Positron Emission Tomography 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 (SUV) were investigated and correlated to clinical outcome measures. Gene expression profiling yielded high-quality data at both time points in 14/18 patients. Unsupervised clustering revealed specific patterns of changes caused by monotherapy vs. combination therapy (p = 0.021, Fisher's exact test). A therapy-induced reduction of known proliferation and hypoxia metagene scores was prominent in the combination arm. Changes in a previously reported hypoxia metagene score were strongly correlated to the objective responses seen by conventional radiology assessments after 6 weeks in the combination arm, Spearman's ρ = 1 (p = 0.017) but not in monotherapy, ρ = −0.029 (p = 1). Similarly, the Predictor Analysis of Microarrays 50 (PAM50) proliferation metagene correlated to tumor changes merely in the combination arm at 6 and 12 weeks (ρ = 0.900, p = 0.083 and ρ = 1, p = 0.017 respectively). Reductions in mean SUV were a reliable early predictor of objective response in monotherapy, ρ = 0.833 (p = 0.008), but not in the combination arm ρ = −0.029 (p = 1). Gene expression profiling of longitudinal metastatic aspiration biopsies was feasible, demonstrated biological validity and provided predictive information. |
| Databáze: | OpenAIRE |
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