title: Using a gene expression signature when controversy exists regarding the indication for adjuvant systemic treatment reduces the proportion of patients receiving adjuvant chemotherapy: a nationwide study.
abstract: The Dutch national guideline advises use of gene-expression signatures, such as the 70-gene signature (70-GS), in case of ambivalence regarding the benefit of adjuvant chemotherapy (CT). In this nationwide study, the impact of 70-GS use on the administration of CT in early breast cancer patients with a dubious indication for CT is assessed.
  
  
  
  Patients within a national guideline directed indication area for 70-GS use who were surgically treated between November 2011 and April 2013 were selected from the Netherlands Cancer Registry database. The effect of 70-GS use on the administration of CT was evaluated in guideline- and age-delineated subgroups addressing potential effect of bias by linear mixed-effect modeling and instrumental variable (IV) analyses.
  
  
  
  A total of 2,043 patients within the indicated area for 70-GS use were included, of whom 298 received a 70-GS. Without use of the 70-GS, 45% of patients received CT. The 70-GS use was associated with a 9.5% decrease in CT administration (95% confidence interval (CI): -15.7 to -3.3%) in linear mixed-effect model analyses and IV analyses showed similar results (-9.9%; 95% CI: -19.3 to -0.4).
  
  
  
  In patients in whom the Dutch national guidelines suggest the use of a gene-expression profile, 70-GS use is associated with a 10% decrease in the administration of adjuvant CT.Genet Med 18 7, 720-726.Genetics in Medicine (2016); 18 7, 720-726. doi:10.1038/gim.2015.152.
authors.affiliation: Department of Surgery, Diakonessenhuis Utrecht, Utrecht, The Netherlands.
authors.forename: A
authors.identifier: 0000-0002-6666-1368
authors.initials: A
authors.lastname: Kuijer
authors.affiliation: Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: A C M
authors.initials: AC
authors.lastname: van Bommel
authors.affiliation: Department of Surgery, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
authors.forename: C A
authors.initials: CA
authors.lastname: Drukker
authors.affiliation: Department of Research, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van der Heiden-van der Loo
authors.affiliation: Department of Medical Oncology, Antoni van Leeuwenhoek Hospital-Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: C H
authors.identifier: 0000-0002-1046-2634
authors.initials: CH
authors.lastname: Smorenburg
authors.affiliation: Department of Pathology, Laboratory for Pathology Dordrecht, Dordrecht, The Netherlands.
authors.forename: P J
authors.identifier: 0000-0002-5509-920X
authors.initials: PJ
authors.lastname: Westenend
authors.affiliation: Department of Medical Oncology, Antoni van Leeuwenhoek Hospital-Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: S C
authors.initials: SC
authors.lastname: Linn
authors.affiliation: Department of Surgery, Antoni van Leeuwenhoek Hospital - Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: E J Th
authors.initials: EJ
authors.lastname: Rutgers
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: S G
authors.initials: SG
authors.lastname: Elias
authors.affiliation: Department of Surgery, Diakonessenhuis Utrecht, Utrecht, The Netherlands.
authors.forename: Th
authors.initials: T
authors.lastname: van Dalen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009426:Netherlands; D059467:Transcriptome / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins