title: BRCA mutations in women with ductal carcinoma in situ.
abstract: OBJECTIVE
  The strength of the association between ductal carcinoma in situ (DCIS) and BRCA mutations has not been defined.
  
  
  METHODS
  Mutation frequency was compared in three groups: (1) a prevalent series of women with DCIS, (2) an incident series of women with DCIS, and (3) a clinic-based series of women with DCIS referred for hereditary cancer risk assessment. In groups 1 and 2, limited to Ashkenazi Jewish (AJ) cases, mutation frequency was compared with that in age-matched AJ controls with invasive breast cancer (IBC).
  
  
  RESULTS
  In group 1, 3 of 62 (4.8%) women with DCIS and 15 of 130 (11.5%) controls with IBC had BRCA mutations. In group 2, 0 of 58 (0%) women with DCIS and 6 of 116 (5.2%) controls with IBC had BRCA mutations [combined odds ratios (OR) in groups 1 and 2: 3.64, 95% confidence interval (95% CI), 1.06-12.46; P=0.04]. In group 3, deleterious mutations were identified in 10 of 79 (12.7%) probands with DCIS, similar to the frequency in IBC probands. In group 3, mutations were associated with family history of ovarian cancer (OR, 13.35; 95% CI, 2.48-71.94; P=0.003) or early onset breast cancer (OR, 16.23; 95% CI, 1.68-157.01; P=0.02) but not with AJ ethnicity or age at diagnosis.
  
  
  CONCLUSIONS
  BRCA mutations were less frequent in women with DCIS not selected for family history or age at diagnosis than in women with IBC. Nonetheless, mutations were found in a significant proportion of women with DCIS who presented for hereditary risk assessment.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Karen Lisa
authors.initials: KL
authors.lastname: Smith
authors.forename: Muriel
authors.initials: M
authors.lastname: Adank
authors.forename: Noah
authors.initials: N
authors.lastname: Kauff
authors.forename: Kelly
authors.initials: K
authors.lastname: Lafaro
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyd
authors.forename: Johanna B
authors.initials: JB
authors.lastname: Lee
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Mark
authors.initials: M
authors.lastname: Robson
mesh_terms: D017668:Age of Onset; D002278:Carcinoma in Situ / Q000235:genetics; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015995:Prevalence; D017384:Sequence Deletion