title: Differences in natural history between breast cancers in BRCA1 and BRCA2 mutation carriers and effects of MRI screening-MRISC, MARIBS, and Canadian studies combined.
abstract: BACKGROUND
  It is recommended that BRCA1/2 mutation carriers undergo breast cancer screening using MRI because of their very high cancer risk and the high sensitivity of MRI in detecting invasive cancers. Clinical observations suggest important differences in the natural history between breast cancers due to mutations in BRCA1 and BRCA2, potentially requiring different screening guidelines.
  
  
  METHODS
  Three studies of mutation carriers using annual MRI and mammography were analyzed. Separate natural history models for BRCA1 and BRCA2 were calibrated to the results of these studies and used to predict the impact of various screening protocols on detection characteristics and mortality.
  
  
  RESULTS
  BRCA1/2 mutation carriers (N = 1,275) participated in the studies and 124 cancers (99 invasive) were diagnosed. Cancers detected in BRCA2 mutation carriers were smaller [80% ductal carcinoma in situ (DCIS) or ≤10 mm vs. 49% for BRCA1, P < 0.001]. Below the age of 40, one (invasive) cancer of the 25 screen-detected cancers in BRCA1 mutation carriers was detected by mammography alone, compared with seven (three invasive) of 11 screen-detected cancers in BRCA2 (P < 0.0001). In the model, the preclinical period during which cancer is screen-detectable was 1 to 4 years for BRCA1 and 2 to 7 years for BRCA2. The model predicted breast cancer mortality reductions of 42% to 47% for mammography, 48% to 61% for MRI, and 50% to 62% for combined screening.
  
  
  CONCLUSIONS
  Our studies suggest substantial mortality benefits in using MRI to screen BRCA1/2 mutation carriers aged 25 to 60 years but show important clinical differences in natural history.
  
  
  CONCLUSIONS
  BRCA1 and BRCA2 mutation carriers may benefit from different screening protocols, for example, below the age of 40.
authors: Department of Public Health, Erasmus MC, Rotterdam, The Netherlands. e.heijnsdijk@erasmusmc.nl
authors: Eveline A M
authors: EA
authors: Heijnsdijk
authors: Ellen
authors: E
authors: Warner
authors: Fiona J
authors: FJ
authors: Gilbert
authors: Madeleine M A
authors: MM
authors: Tilanus-Linthorst
authors: Gareth
authors: G
authors: Evans
authors: Petrina A
authors: PA
authors: Causer
authors: Rosalind A
authors: RA
authors: Eeles
authors: Reinie
authors: R
authors: Kaas
authors: Gerrit
authors: G
authors: Draisma
authors: Elizabeth A
authors: EA
authors: Ramsay
authors: Ruth M L
authors: RM
authors: Warren
authors: Kimberly A
authors: KA
authors: Hill
authors: Nicoline
authors: N
authors: Hoogerbrugge
authors: Martin N J M
authors: MN
authors: Wasser
authors: Elisabeth
authors: E
authors: Bergers
authors: Jan C
authors: JC
authors: Oosterwijk
authors: Maartje J
authors: MJ
authors: Hooning
authors: Emiel J T
authors: EJ
authors: Rutgers
authors: Jan G M
authors: JG
authors: Klijn
authors: Don B
authors: DB
authors: Plewes
authors: Martin O
authors: MO
authors: Leach
authors: Harry J
authors: HJ
authors: de Koning
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D002170:Canada; D055088:Early Detection of Cancer; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D009154:Mutation