title: BRCA-associated breast cancer in young women.
abstract: OBJECTIVE
  To delineate the clinical characteristics and outcomes of breast cancer that arises in the setting of a germline BRCA mutation and to compare BRCA-associated breast cancers (BABC) with those that arise in women without mutations.
  
  
  METHODS
  We reviewed the clinical records of 91 Ashkenazi Jewish women ascertained during studies of the genetics of early-onset breast cancer. All women underwent testing for the BRCA1 mutations 185delAG and 5382insC. After the discovery of BRCA2, 79 women were also tested for the BRCA2 mutation 6174delT.
  
  
  RESULTS
  Mutations were identified in 30 women (33%). BABC were less likely to present with stage I disease than cases in women without mutations (27% v 46%), more likely to have axillary nodal involvement (54% v46%), and more likely to have extensive axillary involvement (25% v 17%). These differences were not statistically significant. BABC were significantly more likely to be histologic grade III (100% v 59%, P=.04) and to be estrogen receptor-negative (70% v 34%, P=.04). In the entire cohort, there were no significant differences between BABC and non-BRCA-associated cancers in 5-year relapse-free survival (65% v 69%, P=not significant [NS]), 5-year event-free survival (57% v 68%, P=NS), or 5-year overall survival. However, among cases diagnosed within 2 years of study entry, there was a trend toward shorter event-free survival in BRCA heterozygotes, but not relapse-free survival. Women with germline BRCA mutations were significantly more likely to develop contralateral breast cancer at 5 years (31% v 4%, P=.0007).
  
  
  CONCLUSIONS
  BABC present with adverse clinical and histopathologic features when compared with cases not associated with BRCA mutations. However, the prognosis of BABC appears to be similar to that of nonassociated cancer. Further studies of incident cases are necessary to define the independent prognostic significance of germline BRCA mutations.
authors.affiliation: Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. robsonm@mskcc.org
authors.forename: M
authors.initials: M
authors.lastname: Robson
authors.forename: T
authors.initials: T
authors.lastname: Gilewski
authors.forename: B
authors.initials: B
authors.lastname: Haas
authors.forename: D
authors.initials: D
authors.lastname: Levin
authors.forename: P
authors.initials: P
authors.lastname: Borgen
authors.forename: P
authors.initials: P
authors.lastname: Rajan
authors.forename: Y
authors.initials: Y
authors.lastname: Hirschaut
authors.forename: P
authors.initials: P
authors.lastname: Pressman
authors.forename: P P
authors.initials: PP
authors.lastname: Rosen
authors.forename: M L
authors.initials: ML
authors.lastname: Lesser
authors.forename: L
authors.initials: L
authors.lastname: Norton
authors.forename: K
authors.initials: K
authors.lastname: Offit
mesh_terms: D000328:Adult; D017668:Age of Onset; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007585:Jews / Q000235:genetics; D008207:Lymphatic Metastasis; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D017421:Sequence Analysis; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D014157:Transcription Factors