title: Selecting Patients with Ovarian Cancer for Germline BRCA Mutation Testing: Findings from Guidelines and a Systematic Literature Review.
abstract: BACKGROUND
  One of the most significant risk factors for the development of ovarian cancer (OC) is a genetic mutation in BRCA1 (breast cancer gene 1) or BRCA2. Here we describe the impact of previous and current guidance on BRCA testing practices and provide evidence about which characteristics best identify patients with OC and an underlying germline BRCA mutation.
  
  
  METHODS
  A search was conducted for guidelines recommending genetic testing to identify constitutional pathogenic mutations in the BRCA genes. In addition, a systematic literature search of studies published in 2003-2015 was performed to assess BRCA mutation frequency in population-based OC patients unselected for patient characteristics (personal history, family history, and Ashkenazi Jewish ethnicity) and to describe the association of patient characteristics with BRCA mutation. Exclusively, studies assessing epithelial OC or invasive epithelial OC with full-gene screening of both BRCA1 and BRCA2 mutations were evaluated.
  
  
  RESULTS
  Of 15 guidelines recommending genetic testing for OC patients, only 5 do not require co-occurrence of specific patient or family characteristics. Twenty-two full publications were identified that assessed germline BRCA mutation frequency in women with OC, utilizing a range of different full mutation detection methods. Germline BRCA mutation prevalence in patients with OC was 5.8-24.8%. Using criteria recommended in guidelines that are yet to be updated, we estimated that 27.5% of all germline BRCA mutations present in patients with OC may be missed because patients do not meet appropriate criteria.
  
  
  CONCLUSIONS
  With the availability of BRCA mutation-targeted therapies, identification of patients with OC with germline BRCA mutations has potential therapeutic consequences. For identified gene carriers, predictive testing to allow cancer prevention strategies, including bilateral salpingo-oophorectomy, provides wider benefit to identifying such gene carriers. Updating guidelines will increase the opportunity for targeted treatment among patients and risk reduction in relatives.
  
  
  BACKGROUND
  AstraZeneca.
authors.affiliation: Somers Cancer Research Building MP 824, University Hospital Southampton, Southampton, UK. d.m.eccles@soton.ac.uk.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Eccles
authors.affiliation: Medical Oncology Department, Vall d'Hebron Hospital and Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Judith
authors.initials: J
authors.lastname: Balmaña
authors.affiliation: AstraZeneca, Cambridge Science Park, Cambridge, UK.
authors.forename: Joe
authors.initials: J
authors.lastname: Clune
authors.affiliation: IMS Health, Munich, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Ehlken
authors.affiliation: IMS Health, Munich, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Gohlke
authors.affiliation: AstraZeneca, Cambridge Science Park, Cambridge, UK.|F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Ceri
authors.initials: C
authors.lastname: Hirst
authors.affiliation: AstraZeneca, Gaithersburg, MD, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Potter
authors.affiliation: IMS Health, Munich, Germany.|Novo Nordisk Pharma GmbH, Mainz, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schroeder
authors.affiliation: AstraZeneca, Gaithersburg, MD, USA.
authors.forename: Jerzy E
authors.initials: JE
authors.lastname: Tyczynski
authors.affiliation: Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Encarnacion B
authors.initials: EB
authors.lastname: Gomez Garcia
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing / Q000592:standards*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics*; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D012307:Risk Factors
keywords: BRCA mutation; Genetic testing guidelines; Oncology; Ovarian cancer