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Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study.
Bancroft, Elizabeth K; Page, Elizabeth C; Castro, Elena; Lilja, Hans; Vickers, Andrew; Sjoberg, Daniel; Assel, Melissa; Foster, Christopher S; Mitchell, Gillian; Drew, Kate; Mæhle, Lovise; Axcrona, Karol; Evans, D Gareth; Bulman, Barbara; Eccles, Diana; McBride, Donna; van Asperen, Christi; Vasen, Hans; Kiemeney, Lambertus A; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Selkirk, Christina; Hulick, Peter J; Bojesen, Anders; Skytte, Anne-Bine; Lam, Jimmy; Taylor, Louise; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A; Oosterwijk, Jan C; Blanco, Ignacio; Salinas, Monica; Cook, Jackie; Rosario, Derek J; Buys, Saundra; Conner, Tom; Ausems, Margreet G; Ong, Kai-ren; Hoffman, Jonathan; Domchek, Susan; Powers, Jacquelyn; Teixeira, Manuel R; Maia, Sofia; Foulkes, William D; Taherian, Nassim; Ruijs, Marielle; Helderman-van den Enden, Apollonia T.
Afiliação
  • Bancroft EK; Cancer Genetics Unit and Academic Urology Unit, Royal Marsden NHS Foundation Trust, London, UK; Oncogenetics Team, Institute of Cancer Research, London, UK.
  • Page EC; Oncogenetics Team, Institute of Cancer Research, London, UK.
  • Castro E; Oncogenetics Team, Institute of Cancer Research, London, UK; Spanish National Cancer Research Centre, Madrid, Spain.
  • Lilja H; Departments of Laboratory Medicine, Surgery, and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Institute of Biomedical Technology, University of Tampere, Tampere, Finland; Department of Laboratory Medi
  • Vickers A; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Sjoberg D; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Assel M; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Foster CS; HCA Healthcare Laboratories, London, WC1E 6JA, UK.
  • Mitchell G; Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
  • Drew K; Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
  • Mæhle L; Norwegian Radium Hospital, Oslo, Norway.
  • Axcrona K; Norwegian Radium Hospital, Oslo, Norway.
  • Evans DG; Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
  • Bulman B; Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
  • Eccles D; Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
  • McBride D; Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
  • van Asperen C; Leiden University Medical Center, Leiden, The Netherlands.
  • Vasen H; Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands.
  • Kiemeney LA; Radboud University Medical Centre, Nijmegen, The Netherlands.
  • Ringelberg J; Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands.
  • Cybulski C; International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
  • Wokolorczyk D; International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
  • Selkirk C; Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, USA.
  • Hulick PJ; Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, USA; Priztker School of Medicine, University of Chicago, Chicago, IL, USA.
  • Bojesen A; Vejle Hospital, Vejle, Denmark.
  • Skytte AB; Vejle Hospital, Vejle, Denmark.
  • Lam J; Department of Urology, Repatriation General Hospital, Daw Park, South Australia, Australia.
  • Taylor L; Department of Urology, Repatriation General Hospital, Daw Park, South Australia, Australia.
  • Oldenburg R; Erasmus Medical Center, Rotterdam, The Netherlands.
  • Cremers R; Radboud University Medical Centre, Nijmegen, The Netherlands.
  • Verhaegh G; Radboud University Medical Centre, Nijmegen, The Netherlands.
  • van Zelst-Stams WA; Radboud University Medical Centre, Nijmegen, The Netherlands.
  • Oosterwijk JC; University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Blanco I; Hereditary Cancer Program, Catalonian Institute of Oncology, L'Hospitalet, Barcelona, Spain.
  • Salinas M; Hereditary Cancer Program, Catalonian Institute of Oncology, L'Hospitalet, Barcelona, Spain.
  • Cook J; Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK.
  • Rosario DJ; Royal Hallamshire Hospital, Sheffield, UK.
  • Buys S; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
  • Conner T; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
  • Ausems MG; Department of Medical Genetics, University Medical Centre Utrecht, The Netherlands.
  • Ong KR; Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham, UK.
  • Hoffman J; Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham, UK.
  • Domchek S; Basser Research Center, University of Pennsylvania, Philadelphia, PA, USA.
  • Powers J; Basser Research Center, University of Pennsylvania, Philadelphia, PA, USA.
  • Teixeira MR; Genetics Department and Research Center, Portuguese Oncology Institute, Porto, Portugal; Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.
  • Maia S; Genetics Department and Research Center, Portuguese Oncology Institute, Porto, Portugal.
  • Foulkes WD; McGill Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Taherian N; McGill Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Ruijs M; The Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Helderman-van den Enden AT; Maastricht University Medical Center, Department of Clinical Genetics, Maastricht, The Netherlands.
Eur Urol ; 66(3): 489-99, 2014 Sep.
Article em En | MEDLINE | ID: mdl-24484606
BACKGROUND: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. OBJECTIVE: To report the first year's screening results for all men at enrollment in the study. DESIGN, SETTING AND PARTICIPANTS: We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrollment, and those men with PSA >3 ng/ml were offered prostate biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. RESULTS AND LIMITATIONS: We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%-double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. CONCLUSIONS: The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. PATIENT SUMMARY: In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Próstata / Neoplasias da Próstata / Antígeno Prostático Específico / Genes BRCA1 / Predisposição Genética para Doença / Genes BRCA2 / Detecção Precoce de Câncer / Mutação Tipo de estudo: Clinical_trials / Diagnostic_studies / Prognostic_studies / Screening_studies Limite: Adult / Aged / Humans / Male / Middle aged Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Próstata / Neoplasias da Próstata / Antígeno Prostático Específico / Genes BRCA1 / Predisposição Genética para Doença / Genes BRCA2 / Detecção Precoce de Câncer / Mutação Tipo de estudo: Clinical_trials / Diagnostic_studies / Prognostic_studies / Screening_studies Limite: Adult / Aged / Humans / Male / Middle aged Idioma: En Ano de publicação: 2014 Tipo de documento: Article