title: BRCA1-associated breast cancers present differently from BRCA2-associated and familial cases: long-term follow-up of the Dutch MRISC Screening Study.
abstract: OBJECTIVE
  The Dutch MRI Screening Study on early detection of hereditary breast cancer started in 1999. We evaluated the long-term results including separate analyses of BRCA1 and BRCA2 mutation carriers and first results on survival.
  
  
  METHODS
  Women with higher than 15% cumulative lifetime risk (CLTR) of breast cancer were screened with biannual clinical breast examination and annual mammography and magnetic resonance imaging (MRI). Participants were divided into subgroups: carriers of a gene mutation (50% to 85% CLTR) and two familial groups with high (30% to 50% CLTR) or moderate risk (15% to 30% CLTR).
  
  
  RESULTS
  Our update contains 2,157 eligible women including 599 mutation carriers (median follow-up of 4.9 years from entry) with 97 primary breast cancers detected (median follow-up of 5.0 years from diagnosis). MRI sensitivity was superior to that of mammography for invasive cancer (77.4% v 35.5%; P<.00005), but not for ductal carcinoma in situ. Results in the BRCA1 group were worse compared to the BRCA2, the high-, and the moderate-risk groups, respectively, for mammography sensitivity (25.0% v 61.5%, 45.5%, 46.7%), tumor size at diagnosis≤1 cm (21.4% v 61.5%, 40.9%, 63.6%), proportion of DCIS (6.5% v 18.8%, 14.8%, 31.3%) and interval cancers (32.3% v 6.3%, 3.7%, 6.3%), and age at diagnosis younger than 30 years (9.7% v 0%). Cumulative distant metastasis-free and overall survival at 6 years in all 42 BRCA1/2 mutation carriers with invasive breast cancer were 83.9% (95% CI, 64.1% to 93.3%) and 92.7% (95% CI, 79.0% to 97.6%), respectively, and 100% in the familial groups (n=43).
  
  
  CONCLUSIONS
  Screening results were somewhat worse in BRCA1 mutation carriers, but 6-year survival was high in all risk groups.
authors.affiliation: Erasmus MC, Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA, Rotterdam, the Netherlands.
authors.forename: Adriana J
authors.initials: AJ
authors.lastname: Rijnsburger
authors.forename: Inge-Marie
authors.initials: IM
authors.lastname: Obdeijn
authors.forename: Reinoutje
authors.initials: R
authors.lastname: Kaas
authors.forename: Madeleine M A
authors.initials: MM
authors.lastname: Tilanus-Linthorst
authors.forename: Carla
authors.initials: C
authors.lastname: Boetes
authors.forename: Claudette E
authors.initials: CE
authors.lastname: Loo
authors.forename: Martin N J M
authors.initials: MN
authors.lastname: Wasser
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bergers
authors.forename: Theo
authors.initials: T
authors.lastname: Kok
authors.forename: Sara H
authors.initials: SH
authors.lastname: Muller
authors.forename: Hans
authors.initials: H
authors.lastname: Peterse
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: Nicoline
authors.initials: N
authors.lastname: Hoogerbrugge
authors.forename: Sybren
authors.initials: S
authors.lastname: Meijer
authors.forename: Carina C M
authors.initials: CC
authors.lastname: Bartels
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Hooning
authors.forename: Mieke
authors.initials: M
authors.lastname: Kriege
authors.forename: Paul I M
authors.initials: PI
authors.lastname: Schmitz
authors.forename: Jan C
authors.initials: JC
authors.lastname: Oosterwijk
authors.forename: Harry J
authors.initials: HJ
authors.lastname: de Koning
authors.forename: Emiel J T
authors.initials: EJ
authors.lastname: Rutgers
authors.forename: Jan G M
authors.initials: JG
authors.lastname: Klijn
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008327:Mammography; D008403:Mass Screening; D008875:Middle Aged; D009154:Mutation; D010808:Physical Examination; D011446:Prospective Studies