title: Assessing early therapeutic response to bevacizumab in primary breast cancer using magnetic resonance imaging and gene expression profiles.
abstract: Antiangiogenic therapy is a promising approach for the treatment of breast cancer. In practice, however, only a subset of patients who receive antiangiogenic drugs demonstrate a significant response. A key challenge, therefore, is to discover biomarkers that are predictive of response to antiangiogenic therapy. To address this issue, we have designed a window-of-opportunity study in which bevacizumab is administered as a short-term first-line treatment to primary breast cancer patients. Central to our approach is the use of a detailed pharmacodynamic assessment, consisting of pre- and post-bevacizumab multi-parametric magnetic resonance imaging scans and core biopsies for exon array gene expression analysis. Here, we illustrate three intrinsic patterns of response to bevacizumab and discuss the molecular mechanisms that may underpin each. Our results illustrate how the combination of dynamic imaging data and gene expression profiles can guide the development of biomarkers for predicting response to antiangiogenic therapy.
authors: University Department of Oncology, Molecular Oncology Laboratories, Medical Oncology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors: Shaveta
authors: S
authors: Mehta
authors: Nicholas P
authors: NP
authors: Hughes
authors: Francesca M
authors: FM
authors: Buffa
authors: Sonia P
authors: SP
authors: Li
authors: Rosemary F
authors: RF
authors: Adams
authors: Asha
authors: A
authors: Adwani
authors: N Jane
authors: NJ
authors: Taylor
authors: Nicola C
authors: NC
authors: Levitt
authors: Anwar R
authors: AR
authors: Padhani
authors: Andreas
authors: A
authors: Makris
authors: Adrian L
authors: AL
authors: Harris
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001707:Biopsy, Needle / Q000379:methods; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D003287:Contrast Media; D005260:Female; D019786:Gadolinium DTPA; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D003287:Contrast Media; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D019786:Gadolinium DTPA