title: Germline BRCA testing is moving from cancer risk assessment to a predictive biomarker for targeting cancer therapeutics.
abstract: OBJECTIVE
  Originally, BRCA testing was used for risk assessment and prevention strategies for breast and ovarian cancer. Nowadays, BRCA status may influence therapeutic decision making at cancer diagnosis. Our objective was to analyze whether the medical advances have changed the burden and pattern of referral, and the pathogenic mutation detection rate.
  
  
  METHODS
  We included 969 probands from our hereditary cancer registry who undertook a full BRCA analysis between 2006 and 2014. Chi-square tests were used to compare categorical variables.
  
  
  RESULTS
  The number of genetic tests have raised from 28 to 170, representing a sixfold increase. In 2006, we tested 1.6 relatives/proband while this proportion was four in 2014. Overall, 20 % harbored a deleterious mutation and 11 % had a variant of unknown significance (VUS). There has been a downward trend in the detection rate of VUS. Testing patients with breast cancer during neoadjuvancy has raised from 4 to 25 % (p = 0.002), while testing them during remission has decreased from 79 to 29 % (p < 0.001). The proportion of patients assessed during the first 6 months after their cancer diagnosis has increased from 3 to 34 % (p = 0.001). Risk reducing mastectomy and salpingoophorectomy have raised from 0 to 24 %, and from 36 to 65 %, respectively.
  
  
  CONCLUSIONS
  BRCA testing has experienced a sixfold increase, the number of relatives being tested has doubled, and the test is being performed at earlier phases of the disease. It is necessary to adequate the health resources to preserve the BRCA genetic counseling quality while incorporating BRCA testing for therapeutic decision making.
authors.affiliation: High Risk and Cancer Prevention Unit, Medical Oncology Department, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, and Vall d'Hebron Institute of Oncology (VHIO), Paseo Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Moreno
authors.affiliation: High Risk and Cancer Prevention Unit, Medical Oncology Department, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, and Vall d'Hebron Institute of Oncology (VHIO), Paseo Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Linossi
authors.affiliation: High Risk and Cancer Prevention Unit, Medical Oncology Department, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, and Vall d'Hebron Institute of Oncology (VHIO), Paseo Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Esteban
authors.affiliation: High Risk and Cancer Prevention Unit, Medical Oncology Department, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, and Vall d'Hebron Institute of Oncology (VHIO), Paseo Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Gadea
authors.affiliation: High Risk and Cancer Prevention Unit, Medical Oncology Department, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, and Vall d'Hebron Institute of Oncology (VHIO), Paseo Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Carrasco
authors.affiliation: Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO) and Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Bonache
authors.affiliation: Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO) and Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Gutiérrez-Enríquez
authors.affiliation: High Risk and Cancer Prevention Unit, Medical Oncology Department, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, and Vall d'Hebron Institute of Oncology (VHIO), Paseo Vall d'Hebron 119-129, 08035, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Cruz
authors.affiliation: Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO) and Universitat Autònoma de Barcelona, Barcelona, Spain.|Clinical and Molecular Genetics Area, University Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Díez
authors.affiliation: High Risk and Cancer Prevention Unit, Medical Oncology Department, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, and Vall d'Hebron Institute of Oncology (VHIO), Paseo Vall d'Hebron 119-129, 08035, Barcelona, Spain. jbalmana@vhio.net.
authors.forename: J
authors.initials: J
authors.lastname: Balmaña
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D003657:Decision Making; D005260:Female; D005500:Follow-Up Studies; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D011379:Prognosis; D012042:Registries; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor
keywords: BRCA; Genetic counseling; Genetic testing; Risk assessment; Therapeutic decision making