title: A simulation model to predict the impact of prophylactic surgery and screening on the life expectancy of BRCA1 and BRCA2 mutation carriers.
abstract: BACKGROUND
  Women with inherited mutations in the BRCA1 or BRCA2 (BRCA1/2) genes are recommended to undergo a number of intensive cancer risk-reducing strategies, including prophylactic mastectomy, prophylactic oophorectomy, and screening. We estimate the impact of different risk-reducing options at various ages on life expectancy.
  
  
  METHODS
  We apply our previously developed Monte Carlo simulation model of screening and prophylactic surgery in BRCA1/2 mutation carriers. Here, we present the mathematical formulation to compute age-specific breast cancer incidence in the absence of prophylactic oophorectomy, which is an input to the simulation model, and provide sensitivity analysis on related model parameters.
  
  
  RESULTS
  The greatest gains in life expectancy result from conducting prophylactic mastectomy and prophylactic oophorectomy immediately after BRCA1/2 mutation testing; these gains vary with age at testing, from 6.8 to 10.3 years for BRCA1 and 3.4 to 4.4 years for BRCA2 mutation carriers. Life expectancy gains from delaying prophylactic surgery by 5 to 10 years range from 1 to 9.9 years for BRCA1 and 0.5 to 4.2 years for BRCA2 mutation carriers. Adding annual breast screening provides gains of 2.0 to 9.9 years for BRCA1 and 1.5 to 4.3 years for BRCA2. Results were most sensitive to variations in our assumptions about the magnitude and duration of breast cancer risk reduction due to prophylactic oophorectomy.
  
  
  CONCLUSIONS
  Life expectancy gains depend on the type of BRCA mutation and age at interventions. Sensitivity analysis identifies the degree of breast cancer risk reduction due to prophylactic oophorectomy as a key determinant of life expectancy gain.
  
  
  CONCLUSIONS
  Further study of the impact of prophylactic oophorectomy on breast cancer risk in BRCA1/2 mutation carriers is warranted.
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Bronislava M
authors.initials: BM
authors.lastname: Sigal
authors.forename: Diego F
authors.initials: DF
authors.lastname: Munoz
authors.forename: Allison W
authors.initials: AW
authors.lastname: Kurian
authors.forename: Sylvia K
authors.initials: SK
authors.lastname: Plevritis
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000517:prevention & control* / Q000601:surgery; D003198:Computer Simulation; D003661:Decision Support Techniques; D005260:Female; D006579:Heterozygote; D006801:Humans; D008017:Life Expectancy; D008408:Mastectomy; D008875:Middle Aged; D015233:Models, Statistical; D010051:Ovarian Neoplasms / Q000235:genetics / Q000517:prevention & control* / Q000601:surgery; D010052:Ovariectomy
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human