title: Detecting Blood-Based Biomarkers in Metastatic Breast Cancer: A Systematic Review of Their Current Status and Clinical Utility.
abstract: Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the available evidence of known blood-based biomarkers in metastatic breast cancer, regarding their clinical utility and state-of-the-art position in the validation process. The initial search yielded 1078 original studies, of which 420 were assessed for eligibility. A total of 320 studies were included in the final synthesis. A Development, Evaluation and Application Chart (DEAC) of all biomarkers was developed. Most studies focus on identifying new biomarkers and search for relations between these biomarkers and traditional molecular characteristics. Biomarkers are usually investigated in only one study (68.8%). Only 9.8% of all biomarkers was investigated in more than five studies. Circulating tumor cells, gene expression within tumor cells and the concentration of secreted proteins are the most frequently investigated biomarkers in liquid biopsies. However, there is a lack of studies focusing on identifying the clinical utility of these biomarkers, by which the additional value still seems to be limited according to the investigated evidence.
authors.affiliation: Health Technology and Services Research, University of Twente, Enschede 7500 AE, The Netherlands. a.m.berghuis@utwente.nl.
authors.forename: A M Sofie
authors.initials: AMS
authors.lastname: Berghuis
authors.affiliation: Health Technology and Services Research, University of Twente, Enschede 7500 AE, The Netherlands. h.koffijberg@utwente.nl.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Koffijberg
authors.affiliation: Biomaterials Science and Technology, University of Twente, Enschede 7500 AE, The Netherlands. j.prakash@utwente.nl.
authors.forename: Jai
authors.initials: J
authors.lastname: Prakash
authors.affiliation: Medical Cell Biophysics, University of Twente, Enschede 7500 AE, The Netherlands. l.w.m.m.terstappen@utwente.nl.
authors.forename: Leon W M M
authors.initials: LW
authors.lastname: Terstappen
authors.affiliation: Health Technology and Services Research, University of Twente, Enschede 7500 AE, The Netherlands. m.j.ijzerman@utwente.nl.
authors.forename: Maarten J
authors.initials: MJ
authors.lastname: IJzerman
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
keywords: blood-based biomarkers; circulating biomarkers; circulating tumor cells (CTCs); development evaluation and application chart (DEAC); developmental stages; liquid biopsy; metastatic breast cancer; utility