title: Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer.
abstract: OBJECTIVE
  To investigate the incidence of germline and somatic BRCA1/2 mutations in unselected patients with triple-negative breast cancer (TNBC) and determine the prognostic significance of carrying a mutation.
  
  
  METHODS
  DNA was obtained from 77 TNBC and normal tissues. BRCA1/2 exons/flanking regions were sequenced from tumor and patients classified as mutant or wild type (WT). Sequencing was repeated from normal tissue to identify germline and somatic mutations. Patient characteristics were compared with chi-square. Survival was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of mutation status with outcome.
  
  
  RESULTS
  Median age was 51 years (27-83 years). Fifteen patients (19.5%) had BRCA mutations: 12 (15.6%) in BRCA1 (one somatic), and 3 (3.9%) in BRCA2. Patients with BRCA mutations tended to be younger than WT, (P = 0.005). Grade, histology, and stage were not associated with mutation status. At a median follow-up of 43 months (7-214 months), there were 33 (42.9%) recurrences and 35 (45.5%) deaths. Five-year recurrence-free survival estimates were 51.7% for WT versus 86.2% for patients with mutations, (P = 0.031); and 5-year overall survival estimates were 52.8% for WT versus 73.3% for patients with mutations (P = 0.225). After adjustment, patients with BRCA mutations had a significantly better RFS (HR: 0.19, 95% CI: 0.045-0.79, P = 0.016) compared with WT.
  
  
  CONCLUSIONS
  In this unselected cohort of TNBC, we found a 19.5% incidence of BRCA mutations. Genetic testing should be discussed with patients with TNBC. Patients with TNBC with BRCA mutations had a significantly lower risk of relapse.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030-4009, USA. agonzalez@mdanderson.org
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Timms
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.forename: Huiqin
authors.initials: H
authors.lastname: Chen
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Litton
authors.forename: Jennifer
authors.initials: J
authors.lastname: Potter
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Lanchbury
authors.forename: Katherine
authors.initials: K
authors.lastname: Stemke-Hale
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Hennessy
authors.forename: Banu K
authors.initials: BK
authors.lastname: Arun
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Kim-Anh
authors.initials: KA
authors.lastname: Do
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D066246:ErbB Receptors