title: Contribution of mammography to MRI screening in BRCA mutation carriers by BRCA status and age: individual patient data meta-analysis.
abstract: BACKGROUND
  We investigated the additional contribution of mammography to screening accuracy in BRCA1/2 mutation carriers screened with MRI at different ages using individual patient data from six high-risk screening trials.
  
  
  METHODS
  Sensitivity and specificity of MRI, mammography and the combination of these tests were compared stratified for BRCA mutation and age using generalised linear mixed models with random effect for studies. Number of screens needed (NSN) for additional mammography-only detected cancer was estimated.
  
  
  RESULTS
  In BRCA1/2 mutation carriers of all ages (BRCA1 = 1,219 and BRCA2 = 732), adding mammography to MRI did not significantly increase screening sensitivity (increased by 3.9% in BRCA1 and 12.6% in BRCA2 mutation carriers, P > 0.05). However, in women with BRCA2 mutation younger than 40 years, one-third of breast cancers were detected by mammography only. Number of screens needed for mammography to detect one breast cancer not detected by MRI was much higher for BRCA1 compared with BRCA2 mutation carriers at initial and repeat screening.
  
  
  CONCLUSIONS
  Additional screening sensitivity from mammography above that from MRI is limited in BRCA1 mutation carriers, whereas mammography contributes to screening sensitivity in BRCA2 mutation carriers, especially those ⩽ 40 years. The evidence from our work highlights that a differential screening schedule by BRCA status is worth considering.
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Postbus 30 001, 9700RB Groningen, The Netherlands.
authors.forename: Xuan-Anh
authors.initials: XA
authors.lastname: Phi
authors.affiliation: Department of Surgical Oncology, Erasmus University Medical Center Rotterdam, Groene Hilledijk 301, 3075EA Rotterdam, The Netherlands.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Saadatmand
authors.affiliation: Department of Epidemiology, University of Groningen, University Medical Center Groningen, Postbus 30 001, 9700RB Groningen, The Netherlands.
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: De Bock
authors.affiliation: Department of Medicine, Division of Medical Oncology, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenua, Toronto, ON, Canada M4N 3M5.
authors.forename: Ellen
authors.initials: E
authors.lastname: Warner
authors.affiliation: On behalf of the HIBCRIT-1 Study, Department of Biomedical Sciences for Health, University of Milan School of Medicine, Scientific Institute (IRCCS) Policlinico San Donato, Unit of Radiology, Via Morandi 30, San Donato Milanese, Milan 20097, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sardanelli
authors.affiliation: On behalf of the MARIBS Study, CRUK Cancer Imaging Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 123 Old Brompton Road, London SW7 3RP, UK.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Leach
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University Vienna, Spitalgasse 23 Vienna 1090, Austria.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Riedl
authors.affiliation: Department of Radiology, Breast Imaging Division, Centre Hospitalier of the University of Montreal (CHUM), Montreal, Tour viger, Pavillion R, 900 Saint Denis Street, Montreal, QC, Canada H2X 0A9.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Trop
authors.affiliation: Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075EA Rotterdam, The Netherlands.
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Hooning
authors.affiliation: Department of Medicine, Division of Medical Oncology, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenua, Toronto, ON, Canada M4N 3M5.
authors.forename: Rodica
authors.initials: R
authors.lastname: Mandel
authors.affiliation: On behalf of the HIBCRIT-1 Study, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Santoro
authors.affiliation: On behalf of the MARIBS Study, CRUK Cancer Imaging Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, 123 Old Brompton Road, London SW7 3RP, UK.
authors.forename: Gek
authors.initials: G
authors.lastname: Kwan-Lim
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University Vienna, Spitalgasse 23 Vienna 1090, Austria.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Helbich
authors.affiliation: On behalf of MRISC Study, Department of Surgical Oncology, Erasmus University Medical Center Rotterdam, Groene Hilledijk 301, 3075EA Rotterdam, The Netherlands.
authors.forename: Madeleine M A
authors.initials: MM
authors.lastname: Tilanus-Linthorst
authors.affiliation: Department of Mathematics and Computer Science, Eindhoven University of Technology, Den Dolech 2, 5600 MB Eindhoven, The Netherlands.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: van den Heuvel
authors.affiliation: Screening and Test Evaluation Program (STEP), School of Public Health, Sydney Medical School, The University of Sydney, Edward Ford Building (A27), Sydney, NSW 2006, Australia.
authors.forename: Nehmat
authors.initials: N
authors.lastname: Houssami
mesh_terms: D000328:Adult; D000367:Age Factors; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008327:Mammography / Q000379:methods; D008875:Middle Aged; D009154:Mutation