title: Annual screening strategies in BRCA1 and BRCA2 gene mutation carriers: a comparative effectiveness analysis.
abstract: BACKGROUND
  Although breast cancer screening with mammography and magnetic resonance imaging (MRI) is recommended for breast cancer-susceptibility gene (BRCA) mutation carriers, there is no current consensus on the optimal screening regimen.
  
  
  METHODS
  The authors used a computer simulation model to compare 6 annual screening strategies (film mammography [FM], digital mammography [DM], FM and magnetic resonance imaging [MRI] or DM and MRI contemporaneously, and alternating FM/MRI or DM/MRI at 6-month intervals) beginning at ages 25 years, 30 years, 35 years, and 40 years, and 2 strategies of annual MRI with delayed alternating DM/FM versus clinical surveillance alone. Strategies were evaluated without and with mammography-induced breast cancer risk using 2 models of excess relative risk. Input parameters were obtained from the medical literature, publicly available databases, and calibration.
  
  
  RESULTS
  Without radiation risk effects, alternating DM/MRI starting at age 25 years provided the highest life expectancy (BRCA1, 72.52 years, BRCA2, 77.63 years). When radiation risk was included, a small proportion of diagnosed cancers was attributable to radiation exposure (BRCA1, <2%; BRCA2, <4%). With radiation risk, alternating DM/MRI at age 25 years or annual MRI at age 25 years/delayed alternating DM at age 30 years was the most effective, depending on the radiation risk model used. Alternating DM/MRI starting at age 25 years also produced the highest number of false-positive screens per woman (BRCA1, 4.5 BRCA2, 8.1).
  
  
  CONCLUSIONS
  Annual MRI at age 25 years/delayed alternating DM at age 30 years is probably the most effective screening strategy in BRCA mutation carriers. Screening benefits, associated risks, and personal acceptance of false-positive results should be considered in choosing the optimal screening strategy for individual women.
authors.affiliation: Massachusetts General Hospital Institute for Technology Assessment, Boston, Massachusetts, USA.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Lowry
authors.forename: Janie M
authors.initials: JM
authors.lastname: Lee
authors.forename: Chung Y
authors.initials: CY
authors.lastname: Kong
authors.forename: Pamela M
authors.initials: PM
authors.lastname: McMahon
authors.forename: Michael E
authors.initials: ME
authors.lastname: Gilmore
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Cott Chubiz
authors.forename: Etta D
authors.initials: ED
authors.lastname: Pisano
authors.forename: Constantine
authors.initials: C
authors.lastname: Gatsonis
authors.forename: Paula D
authors.initials: PD
authors.lastname: Ryan
authors.forename: Elissa M
authors.initials: EM
authors.lastname: Ozanne
authors.forename: G Scott
authors.initials: GS
authors.lastname: Gazelle
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008017:Life Expectancy; D008279:Magnetic Resonance Imaging; D008327:Mammography / Q000009:adverse effects; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology; D012680:Sensitivity and Specificity