title: Breast density as indicator for the use of mammography or MRI to screen women with familial risk for breast cancer (FaMRIsc): a multicentre randomized controlled trial.
abstract: BACKGROUND
  To reduce mortality, women with a family history of breast cancer often start mammography screening at a younger age than the general population. Breast density is high in over 50% of women younger than 50 years. With high breast density, breast cancer incidence increases, but sensitivity of mammography decreases. Therefore, mammography might not be the optimal method for breast cancer screening in young women. Adding MRI increases sensitivity, but also the risk of false-positive results. The limitation of all previous MRI screening studies is that they do not contain a comparison group; all participants received both MRI and mammography. Therefore, we cannot empirically assess in which stage tumours would have been detected by either test.The aim of the Familial MRI Screening Study (FaMRIsc) is to compare the efficacy of MRI screening to mammography for women with a familial risk. Furthermore, we will assess the influence of breast density.
  
  
  METHODS
  This Dutch multicentre, randomized controlled trial, with balanced randomisation (1:1) has a parallel grouped design. Women with a cumulative lifetime risk for breast cancer due to their family history of ≥20%, aged 30-55 years are eligible. Identified BRCA1/2 mutation carriers or women with 50% risk of carrying a mutation are excluded. Group 1 receives yearly mammography and clinical breast examination (n = 1000), and group 2 yearly MRI and clinical breast examination, and mammography biennially (n = 1000).Primary endpoints are the number and stage of the detected breast cancers in each arm. Secondary endpoints are the number of false-positive results in both screening arms. Furthermore, sensitivity and positive predictive value of both screening strategies will be assessed. Cost-effectiveness of both strategies will be assessed. Analyses will also be performed with mammographic density as stratification factor.
  
  
  CONCLUSIONS
  Personalized breast cancer screening might optimize mortality reduction with less over diagnosis. Breast density may be a key discriminator for selecting the optimal screening strategy for women < 55 years with familial breast cancer risk; mammography or MRI. These issues are addressed in the FaMRIsc study including high risk women due to a familial predisposition.
  
  
  BACKGROUND
  Netherland Trial Register NTR2789.
authors.affiliation: Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. s.saadatmand@erasmusmc.nl
authors.forename: Sepideh
authors.initials: S
authors.lastname: Saadatmand
authors.forename: Emiel J T
authors.initials: EJ
authors.lastname: Rutgers
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: Hermien M
authors.initials: HM
authors.lastname: Zonderland
authors.forename: Margreet G E M
authors.initials: MG
authors.lastname: Ausems
authors.forename: Kristien B M I
authors.initials: KB
authors.lastname: Keymeulen
authors.forename: Margreet S
authors.initials: MS
authors.lastname: Schlooz-Vries
authors.forename: Linetta B
authors.initials: LB
authors.lastname: Koppert
authors.forename: Eveline A M
authors.initials: EA
authors.lastname: Heijnsdijk
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Cees
authors.initials: C
authors.lastname: Verhoef
authors.forename: Jan C
authors.initials: JC
authors.lastname: Oosterwijk
authors.forename: Inge-Marie
authors.initials: IM
authors.lastname: Obdeijn
authors.forename: Harry J
authors.initials: HJ
authors.lastname: de Koning
authors.forename: Madeleine M A
authors.initials: MM
authors.lastname: Tilanus-Linthorst
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging; D002985:Clinical Protocols; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008327:Mammography; D008875:Middle Aged; D012307:Risk Factors