title: Magnetic resonance imaging improves breast screening sensitivity in BRCA mutation carriers age ≥ 50 years: evidence from an individual patient data meta-analysis.
abstract: OBJECTIVE
  There is no consensus on whether magnetic resonance imaging (MRI) should be included in breast screening protocols for women with BRCA1/2 mutations age ≥ 50 years. Therefore, we investigated the evidence on age-related screening accuracy in women with BRCA1/2 mutations using individual patient data (IPD) meta-analysis.
  
  
  METHODS
  IPD were pooled from six high-risk screening trials including women with BRCA1/2 mutations who had completed at least one screening round with both MRI and mammography. A generalized linear mixed model with repeated measurements and a random effect of studies estimated sensitivity and specificity of MRI, mammography, and the combination in all women and specifically in those age ≥ 50 years.
  
  
  RESULTS
  Pooled analysis showed that in women age ≥ 50 years, screening sensitivity was not different from that in women age < 50 years, whereas screening specificity was. In women age ≥ 50 years, combining MRI and mammography significantly increased screening sensitivity compared with mammography alone (94.1%; 95% CI, 77.7% to 98.7% v 38.1%; 95% CI, 22.4% to 56.7%; P < .001). The combination was not significantly more sensitive than MRI alone (94.1%; 95% CI, 77.7% to 98.7% v 84.4%; 95% CI, 61.8% to 94.8%; P = .28). Combining MRI and mammography in women age ≥ 50 years resulted in sensitivity similar to that in women age < 50 years (94.1%; 95% CI, 77.7% to 98.7% v 93.2%; 95% CI, 79.3% to 98%; P = .79).
  
  
  CONCLUSIONS
  Addition of MRI to mammography for screening BRCA1/2 mutation carriers age ≥ 50 years improves screening sensitivity by a magnitude similar to that observed in younger women. Limiting screening MRI in BRCA1/2 carriers age ≥ 50 years should be reconsidered.
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Xuan-Anh
authors.initials: XA
authors.lastname: Phi
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Nehmat
authors.initials: N
authors.lastname: Houssami
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Inge-Marie
authors.initials: IM
authors.lastname: Obdeijn
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Ellen
authors.initials: E
authors.lastname: Warner
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sardanelli
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Leach
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Riedl
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Trop
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Madeleine M A
authors.initials: MM
authors.lastname: Tilanus-Linthorst
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Rodica
authors.initials: R
authors.lastname: Mandel
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Filippo
authors.initials: F
authors.lastname: Santoro
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Gek
authors.initials: G
authors.lastname: Kwan-Lim
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Helbich
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: de Koning
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Van den Heuvel
authors.affiliation: Xuan-Anh Phi, Edwin R. Van den Heuvel, and Geertruida H. de Bock, University of Groningen, University Medical Center Groningen, Groningen; Inge-Marie Obdeijn, Madeleine M.A. Tilanus-Linthorst, and Harry J. de Koning, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands; Nehmat Houssami, School of Public Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Ellen Warner and Rodica Mandel, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario; Isabelle Trop, Hospital of Montreal, Montreal, Quebec, Canada; Francesco Sardanelli, University of Milan School of Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, Milan; Filippo Santoro, Istituto Superiore di Sanità, Rome, Italy; Martin O. Leach and Gek Kwan-Lim, Institute of Cancer Research and Royal Marsden National Health Service Foundation Trust, London, United Kingdom; and Christopher C. Riedl and Thomas H. Helbich, Medical University Vienna, Vienna, Austria. g.h.de.bock@umcg.nl.
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008327:Mammography / Q000379:methods; D008875:Middle Aged; D009154:Mutation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein