title: Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population.
abstract: In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast cancer patients, unselected for family history, diagnosed in a cancer hospital before the age of 50 years in 1974-2002; most prevalent Dutch pathogenic BRCA1/2 mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%) of the patients were proven to be BRCA1/2 mutation carriers. We found that 78% and 69% of BRCA1 and BRCA2 mutation carriers identified met the criteria for referral to the CGC based on age, family history and synchronous multiple tumors; reflected by a combined sensitivity of 75.5% and specificity of 63.2%. More than half of the BRCA1 mutation carriers, that is, 58% had a triple-negative tumor. The highest AUC was obtained by shifting the age at diagnosis threshold criterion from 40 to 35 years and by adding a 'triple-negative breast cancer' criterion with an age threshold of 45 years; the specificity increased to 71.2%, whereas the sensitivity remained the same; that is, a referral of fewer patients will lead to the identification of at least the same number of BRCA1/2 mutation carriers. Two-thirds of the BRCA1/2 mutation carriers identified in this research setting had been referred for counseling and testing. Our results indicate that, awaiting a possibly more extended mutation screening of all breast cancer patients, the triple-negative status of a breast cancer should be added to the CGC referral criteria.
authors.affiliation: 1] Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands [2] Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: van den Broek
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Karen
authors.initials: K
authors.lastname: de Ruiter
authors.affiliation: Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van 't Veer
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.affiliation: Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Senno
authors.initials: S
authors.lastname: Verhoef
authors.affiliation: 1] Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands [2] Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Marjanka K
authors.initials: MK
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009426:Netherlands / Q000453:epidemiology; D012017:Referral and Consultation; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor