Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers : Results from the initial screening round of the IMPACT study
Bancroft, Elizabeth (Institute of Cancer Research (Londres, Regne Unit))
Page, Elizabeth C. (Institute of Cancer Research (Londres, Regne Unit))
Castro, Elena (Centro Nacional de Investigaciones Oncológicas)
Lilja, Hans (Lund University (Lund, Suècia))
Vickers, Andrew J. (Memorial Sloan Kettering Cancer Center)
Sjoberg, Daniel (Memorial Sloan Kettering Cancer Center)
Assel, Melissa (Memorial Sloan Kettering Cancer Center)
Foster, Christopher (HCA Healthcare Laboratories (Londres, Regne Unit))
Mitchell, Gillian (University of Melbourne (Melbourne, Austràlia))
Drew, Kate (Peter MacCallum Cancer Centre (Melbourne, Austràlia))
Maehle, Lovise Olaug (Norwegian Radium Hospital (Oslo, Noruega))
Axcrona, Karol (Norwegian Radium Hospital (Oslo, Noruega))
Evans, Gareth (Central Manchester University Hospitals NHS Foundation Trust (Manchester, Anglaterra))
Bulman, Barbara (Central Manchester University Hospitals NHS Foundation Trust (Manchester, Anglaterra))
Eccles, Diana M. (Princess Anne Hospital (Southampton, Anglaterra))
McBride, Donna (Princess Anne Hospital (Southampton, Anglaterra))
Van Asperen, Christi J. (Leiden University Medical Center)
Vasen, Hans (Foundation for the Detection of Hereditary Tumours (Leiden, Països Baixos))
Kiemeney, Lambertus (Radboud University Medical Centre (Nijmegen, Països Baixos))
Ringelberg, Janneke (Foundation for the Detection of Hereditary Tumours (Leiden, Països Baixos))
Cybulski, Cezary (Pomeranian Medical University (Szczecin, Polònia))
Wokolorczyk, Dominika (Pomeranian Medical University (Szczecin, Polònia))
Selkirk, Christina (NorthShore University HealthSystem (Evanston, Estats Units d'Amèrica))
Hulick, Peter J. (University of Chicago (Chicago, Estats Units d'Amèrica))
Bojesen, Anders (Vejle Hospital (Vejle, Dinamarca))
Skytte, Anne-Bine (Vejle Hospital (Vejle, Dinamarca))
Lam, Jimmy (Repatriation General Hospital (Austràlia))
Taylor, Louise (Repatriation General Hospital (Austràlia))
Oldenburg, Rogier A. (Erasmus Medical Center)
Cremers, Ruben (Radboud University Medical Centre (Nijmegen, Països Baixos))
Verhaegh, Gerald (Radboud University Medical Centre (Nijmegen, Països Baixos))
Van Zelst-Stams, Wendy A. (Radboud University Medical Centre (Nijmegen, Països Baixos))
Oosterwijk, Jan C. (University of Groningen (Groningen, Països Baixos))
Blanco Guillermo, Ignacio (Institut Català d'Oncologia (Barcelona))
Salinas, Monica (Institut Català d'Oncologia (Barcelona))
Cook, Jacqueline A. (Sheffield Children's Hospital (Sheffield, Anglaterra))
Rosario, Derek J. (Royal Hallamshire Hospital (Sheffield, Anglaterra))
Buys, Sandra S. (University of Utah (Utah, Estats Units d'Amèrica))
Conner, Thomas A. (University of Utah (Utah, Estats Units d'Amèrica))
Ausems, Margreet (University Medical Centre Utrecht (Utrecht, Països Baixos))
Ong, Kairen (Birmingham Women's Hospital)
Hoffman, Jonathan (Birmingham Women's Hospital)
Domchek, Susan M (University of Pennsylvania (Pennsilvània, Estats Units d'Amèrica))
Powers, Jacquelyn M. (University of Pennsylvania (Pennsilvània, Estats Units d'Amèrica))
Teixeira, Manuel R. (Porto University (Porto, Portugal))
Maia, Sofia F. (Portuguese Oncology Institute (Porto, Portugal))
Foulkes, William (McGill University (Quebec, Canadà))
Taherian, Nassim (McGill University (Quebec, Canadà))
Ruijs, Marielle (The Netherlands Cancer Institute (Amsterdam, Països Baixos))
Den Enden, Apollonia T. Helderman-van (Maastricht University Medical Center (Maastricht, Països Baixos))
Izatt, Louise (South East Thames Genetics Service (Londres, Regne Unit))
Davidson, Rosemarie H. (Yorkhill NHS Trust (Glasgow, Escòcia))
Adank, Muriel A. (University Medical Center (Amsterdam, Països Baixos))
Walker, Lisa J. (Churchill Hospital (Oxford, Regne Unit))
Schmutzler, Rita (Uniklinik Köln (Colònia, Alemanya))
Tucker, Kathy M. (University of New South Wales (Sydney, Austràlia))
Kirk, Judy (University of Sydney (Sydney, Austràlia))
Hodgson, Shirley Victoria (St. George's Hospital (Londres, Anglaterra))
Harris, Marion T. (Monash Health (Victòria, Autràlia))
Douglas, Fiona S. (Newcastle Upon Tyne Hospitals NHS Trust (Newcastle, Regne Unit))
Lindeman, Geoffrey J. (University of Melbourne (Melbourne, Austràlia))
Zgajnar, Janez (Institute of Oncology (Ljubljana, Eslovènia))
Tischkowitz, Marc D. (University of Cambridge (Cambridge, Regne Unit))
Clowes, Virginia E. (University of Cambridge (Cambridge, Regne Unit))
Susman, Rachel (Royal Brisbane and Women's Hospital (Queensland, Austràlia))
Ramon y Cajal, Teresa (Institut d'Investigació Biomèdica Sant Pau)
Patcher, Nicholas (University of Western Australia (Perth, Austràlia))
Gadea, Neus (Hospital Universitari Vall d'Hebron)
Spigelman, Allan (St. Vincent's Hospital (Sydney, Austràlia))
Van Os, Theo (Academic Medical Center (Amsterdam, Països Baixos))
Liljegren, Annelie (Karolinska University Hospital)
Side, Lucy E. (Institute of Child Health (Londres, Anglaterra))
Brewer, Carole M. (Royal Devon and Exeter Hospital (Exeter, Regne Unit))
Brady, Angela F. (North West London Hospitals NHS Trust (Harrow, Regne Unit))
Donaldson, Alan (St. Michael's Hospital (Bristol, Regne Unit))
Stefansdottir, Vigdis (Landspitali University Hospital (Reykjavík, Islàndia))
Friedman, Eitan A. (Chaim Shema Medical Center (Israel))
Chen-Shtoyerman, Rakefet (Kaplan Medical Center (Israel))
Amor, David (Murdoch Childrens Research Institute (Victòria, Austràlia))
Copakova, Lucia (National Cancer Institute (Bratislava, Eslovàquia))
Barwell, Julian G. (University Hospitals Leicester (Leicester, Regne Unit))
Giri, Veda (Fox Chase Cancer Center (Filadèlfia, Estats Units d'Amèrica))
Murthy, Vedang (Tata Memorial Centre (Bombai, Índia))
Nicolai, Nicola (Istituto Nazionale dei Tumori (Milà, Itàlia))
Teo, Soo (Subang Jaya Medical Centre (Selangor, Malàisia))
Greenhalgh, Lynn (Royal Liverpool Children's Hospital (Liverpool, Regne Unit))
Strom, Sara S. (University of Texas (Texas, Estats Units d'Amèrica))
Henderson, Alex (Newcastle Upon Tyne Hospitals NHS Trust (Newcastle, Regne Unit))
McGrath, John (Royal Devon and Exeter Hospital (Exeter, Regne Unit))
Gallagher, David James (Mater Misericordiae University Hospital (Dublín, Irlanda))
Aaronson, Neil K. (The Netherlands Cancer Institute (Amsterdam, Països Baixos))
Ardern-Jones, Audrey T. (The Royal Marsden NHS Foundation Trust)
Bangma, Chris H. (Erasmus Medical Center)
Dearnaley, David P. (Institute of Cancer Research (Londres, Regne Unit))
Costello, Philandra (Princess Anne Hospital (Southampton, Regne Unit))
Eyfjord, Jórunn Erla (University of Iceland (Reykjavík, Islàndia))
Rothwell, Jeanette (Central Manchester University Hospitals NHS Foundation Trust (Manchester, Regne Unit))
Falconer, Alison (Imperial College Healthcare NHS Trust (Londres, Regne Unit))
Gronberg, Henrik (University Hospital (Umea, Suècia))
Hamdy, Freddie C (Churchill Hospital (Oxford, Regne Unit))
Johannsson, Óskar Th. (Landspitali University Hospital (Reykjavík, Islàndia))
Khoo, Vincent S. (The Royal Marsden NHS Foundation Trust)
Kote-Jarai, Zsofia S. (Institute of Cancer Research (Londres, Regne Unit))
Lubinski, Jan (Pomeranian Medical University (Szczecin, Polònia))
Axcrona, Ulrika (Norwegian Radium Hospital (Oslo, Noruega))
Melia, Jane Westfield (University of Cambridge (Cambridge, Regne Unit))
McKinley, Joanne M. (Peter MacCallum Cancer Centre (Victòria, Austràlia))
Mitra, Anita Vanessa (University College London Hospitals NHS Foundation Trust (Londres, Regne Unit))
Moynihan, Clare (Institute of Cancer Research (Londres, Regne Unit))
Rennert, Gad (Carmel Medical Center (Haifa, Israel))
Suri, Mohnish (Nottingham City Hospital (Nottingham, Regne Unit))
Wilson, Penny (BioZenix (Cheshire, Regne Unit))
Killick, Emma (Institute of Cancer Research (Londres, Regne Unit))
Moss, Susan Mary (Queen Mary University of London (Londres, Regne Unit))
Eeles, Rosalind (Institute of Cancer Research (Londres, Regne Unit))
Universitat Autònoma de Barcelona

Data:	2014
Resum:	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 enrolment 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 enrolment, 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. © 2014 European Association of Urology.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	BRCA1 ; BRCA2 ; Prostate cancer ; Prostate-specific antigen ; Targeted screening
Publicat a:	European Urology, Vol. 66 Núm. 3 (september 2014) , p. 489-499, ISSN 1873-7560

DOI: 10.1016/j.eururo.2014.01.003
PMID: 24484606

13 p, 2.0 MB

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