title: Limited family structure and triple-negative breast cancer (TNBC) subtype as predictors of BRCA mutations in a genetic counseling cohort of early-onset sporadic breast cancers.
abstract: Early-onset diagnosis is an eligibility criterion for BRCA1 and BRCA2 (BRCA) testing in sporadic breast cancer patients. Limited family structure has been proposed as a predictor of BRCA mutation status in this group of patients. An overwhelming amount of data supports a strong association between BRCA1 mutations and triple-negative breast cancer (TNBC). Here, we analyze the feasibility of using limited family structure and TNBC as predictors of BRCA mutation status in early-onset breast cancer patients attending genetic counseling units. We have conducted the study in a cohort of sporadic early-onset (≤35 years) breast cancer patients (N = 341) previously selected for BRCA genetic testing in Academic Hereditary Cancer Clinics from Spain. A retrospective review of medical records available at the time of risk assessment allowed us classifying patients according to family structure and TNBC. In addition, BRCAPRO score was calculated for all patients. Association between categorical variables was investigated using the Fisher's exact test. Binary Logistic Regression Analysis was used for multivariate analysis. Limited family structure (OR 3.61, p = 0.013) and TNBC (OR 3.14, p = 0.013) were independent predictors of BRCA mutation status. Mutation prevalence in the subgroup of patients with at least one positive predictor was 14%, whereas it dropped to 3% in non-TNBCs with adequate family history (OR 5.31, 95% CI 1.38-23.89, p = 0.006). BRCAPRO correctly discerned between limited and adequate family structures. Limited family structure and TNBC are feasible predictors of BRCA mutation status in sporadic early-onset (≤35 years) breast cancer patients attending genetic counseling units. The low prevalence of mutations observed in non-TNBCs with adequate family structure suggests that this subgroup of patients might be excluded from genetic testing.
authors.affiliation: Genetic Counseling Unit, Department of Clinical Oncology, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Jon
authors.initials: J
authors.lastname: Zugazagoitia
authors.forename: Pedro
authors.initials: P
authors.lastname: Pérez-Segura
authors.forename: Arancha
authors.initials: A
authors.lastname: Manzano
authors.forename: Ignacio
authors.initials: I
authors.lastname: Blanco
authors.forename: Ana
authors.initials: A
authors.lastname: Vega
authors.forename: Ana
authors.initials: A
authors.lastname: Custodio
authors.forename: Alex
authors.initials: A
authors.lastname: Teulé
authors.forename: Laura
authors.initials: L
authors.lastname: Fachal
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martínez
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento
authors.forename: Juan Jesús
authors.initials: JJ
authors.lastname: Cruz-Hernández
authors.forename: Isabel
authors.initials: I
authors.lastname: Chirivella
authors.forename: Vicente
authors.initials: V
authors.lastname: Garcés
authors.forename: Pilar
authors.initials: P
authors.lastname: Garre
authors.forename: Atocha
authors.initials: A
authors.lastname: Romero
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Hoya
mesh_terms: D000328:Adult; D017668:Age of Onset; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005191:Family Characteristics; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D006801:Humans; D007124:Immunoenzyme Techniques; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013030:Spain / Q000453:epidemiology; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C492913:BRCA1 protein, human; C551750:BRCA2 protein, human; C508053:ERBB2 protein, human