Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study

Elizabeth K. Bancroft; Elizabeth C. Page; Elena Castro; Hans Lilja; Andrew Vickers; Daniel Sjoberg; Melissa Assel; Christopher S. Foster; Gillian Mitchell; Kate Drew; Lovise Mæhle; Karol Axcrona; D. Gareth Evans; Barbara Bulman; Diana Eccles; Donna McBride; Christi van Asperen; Hans Vasen; Lambertus A. Kiemeney; Janneke Ringelberg; Cezary Cybulski; Dominika Wokolorczyk; Christina Selkirk; Peter J. Hulick; Anders Bojesen; Anne-Bine Skytte; Jimmy Lam; Louise Taylor; Rogier Oldenburg; Ruben Cremers; Gerald Verhaegh; Wendy A. van Zelst-Stams; Jan C. Oosterwijk; Ignacio Blanco; Monica Salinas; Jackie Cook; Derek J. Rosario; Saundra Buys; Tom Conner; Margreet G. Ausems; Kai-ren Ong; Jonathan Hoffman; Susan Domchek; Jacquelyn Powers; Manuel R. Teixeira; Sofia Maia; William D. Foulkes; Nassim Taherian; Marielle Ruijs; Apollonia T. Helderman-van den Enden; Louise Izatt; Rosemarie Davidson; Muriel A. Adank; Lisa Walker; Rita Schmutzler; Kathy Tucker; Judy Kirk; Shirley Hodgson; Marion Harris; Fiona Douglas; Geoffrey J. Lindeman; Janez Zgajnar; Marc Tischkowitz; Virginia E. Clowes; Rachel Susman; Teresa Ramón y Cajal; Nicholas Patcher; Neus Gadea; Allan Spigelman; Theo van Os; Annelie Liljegren; Lucy Side; Carole Brewer; Angela F. Brady; Alan Donaldson; Vigdis Stefansdottir; Eitan Friedman; Rakefet Chen-Shtoyerman; David J. Amor; Lucia Copakova; Julian Barwell; Veda N. Giri; Vedang Murthy; Nicola Nicolai; Soo-Hwang Teo; Lynn Greenhalgh; Sara Strom; Alex Henderson; John McGrath; David Gallagher; Neil Aaronson; Audrey Ardern-Jones; Chris Bangma; David Dearnaley; Philandra Costello; Jorunn Eyfjord; Jeanette Rothwell; Alison Falconer; Henrik Gronberg; Freddie C. Hamdy; Oskar Johannsson; Vincent Khoo; Zsofia Kote-Jarai; Jan Lubinski; Ulrika Axcrona; Jane Melia; Joanne McKinley; Anita V. Mitra; Clare Moynihan; Gad Rennert; Mohnish Suri; Penny Wilson; Emma Killick; Sue Moss; Rosalind A. Eeles; The IMPACT Collaborators; Christine June Jacobs

doi:10.1016/j.eururo.2014.01.003

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Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study

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Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study

Elizabeth K. Bancroft, Elizabeth C. Page, Elena Castro, Hans Lilja, Andrew Vickers, Daniel Sjoberg, Melissa Assel, Christopher S. Foster, Gillian Mitchell, Kate Drew, …

European urology, Vol.66(3), pp.489-499

01/09/2014

DOI: https://doi.org/10.1016/j.eururo.2014.01.003

PMID: 24484606

Abstract

BRCA1

BRCA2

Prostate cancer

Prostate-specific antigen

Targeted screening

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. To report the first year's screening results for all men at enrolment in the study. 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. 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. 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. 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. 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. This report demonstrates that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these higher-risk men resulted in the identification of tumours that were more likely to require treatment.

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Title: Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study
Creators: Elizabeth K. Bancroft - Royal Marsden NHS Foundation Trust
Elizabeth C. Page - TEAM
Elena Castro - TEAM
Hans Lilja - Lund University
Andrew Vickers - Memorial Sloan Kettering Cancer Center
Daniel Sjoberg - Memorial Sloan Kettering Cancer Center
Melissa Assel - Memorial Sloan Kettering Cancer Center
Christopher S. Foster - HCA Healthcare
Gillian Mitchell - University of Melbourne
Kate Drew - Peter MacCallum Cancer Centre
Lovise Mæhle - Norwegian Radium Hospital, Oslo, Norway
Karol Axcrona - Norwegian Radium Hospital, Oslo, Norway
D. Gareth Evans - Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
Barbara Bulman - Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
Diana Eccles - Princess Anne Hospital
Donna McBride - Princess Anne Hospital
Christi van Asperen - Leiden University Medical Center
Hans Vasen - Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands
Lambertus A. Kiemeney - Radboud University Nijmegen
Janneke Ringelberg - Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands
Cezary Cybulski - Pomeranian Medical University
Dominika Wokolorczyk - Pomeranian Medical University
Christina Selkirk - NorthShore University HealthSystem
Peter J. Hulick - University of Chicago
Anders Bojesen - Vejle Hospital, Vejle, Denmark
Anne-Bine Skytte - Vejle Hospital, Vejle, Denmark
Jimmy Lam - Repatriation General Hospital
Louise Taylor - Repatriation General Hospital
Rogier Oldenburg - Erasmus University Rotterdam
Ruben Cremers - Radboud University Medical Centre, Nijmegen, The Netherlands
Gerald Verhaegh - Radboud University Nijmegen
Wendy A. van Zelst-Stams - Radboud University Nijmegen
Jan C. Oosterwijk - University Medical Center Groningen
Ignacio Blanco - Hereditary Cancer Program, Catalonian Institute of Oncology, L’Hospitalet, Barcelona, Spain
Monica Salinas - Hereditary Cancer Program, Catalonian Institute of Oncology, L’Hospitalet, Barcelona, Spain
Jackie Cook - Boston Children's Museum
Derek J. Rosario - Royal Hallamshire Hospital
Saundra Buys - Huntsman Cancer Institute
Tom Conner - Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
Margreet G. Ausems - Department of Medical Genetics, University Medical Centre Utrecht, The Netherlands
Kai-ren Ong - Birmingham Women's Hospital
Jonathan Hoffman - Birmingham Women's Hospital
Susan Domchek - University of Pennsylvania
Jacquelyn Powers - University of Pennsylvania
Manuel R. Teixeira - Genetics Department and Research Center, Portuguese Oncology Institute, Porto, Portugal
Sofia Maia - Genetics Department and Research Center, Portuguese Oncology Institute, Porto, Portugal
William D. Foulkes - McGill University
Nassim Taherian - McGill University
Marielle Ruijs - The Netherlands Cancer Institute, Amsterdam, The Netherlands
Apollonia T. Helderman-van den Enden - Maastricht University
Louise Izatt - Guy's Hospital
Rosemarie Davidson - Duncan Guthrie Institute of Medical Genetics, Yorkhill NHS Trust, Glasgow, UK
Muriel A. Adank - Amsterdam UMC Location VUmc
Lisa Walker - Churchill Hospital
Rita Schmutzler - University Hospital Cologne
Kathy Tucker - UNSW Sydney
Judy Kirk - University of Sydney
Shirley Hodgson - St George's Hospital
Marion Harris - Monash Health
Fiona Douglas - Northern Genetics Service, Newcastle upon Tyne Hospitals, Newcastle upon Tyne, UK
Geoffrey J. Lindeman - University of Melbourne
Janez Zgajnar - Institute of Oncology Ljubljana
Marc Tischkowitz - University of Cambridge
Virginia E. Clowes - University of Cambridge
Rachel Susman - Royal Brisbane and Women's Hospital
Teresa Ramón y Cajal - Hospital de Sant Pau
Nicholas Patcher - University of Western Australia
Neus Gadea - Hospital Vall d’Hebron, Barcelona, Spain
Allan Spigelman - St. Vincent's Birmingham
Theo van Os - Academic Medical Center
Annelie Liljegren - Karolinska University Hospital
Lucy Side - Institute of Child Health
Carole Brewer - Derriford Hospital
Angela F. Brady - London North West Healthcare NHS Trust
Alan Donaldson - St Michael's Hospital
Vigdis Stefansdottir - Reykjavík University
Eitan Friedman - Chaim Shema Medical Center, Tel-Hashomer, Israel
Rakefet Chen-Shtoyerman - Kaplan Medical Center
David J. Amor - Murdoch Childrens Research Institute, Parkville, Victoria, Australia
Lucia Copakova - National Cancer Institute, Bratislava, Slovak Republic
Julian Barwell - University of Leicester
Veda N. Giri - Fox Chase Cancer Center
Vedang Murthy - Tata Memorial Hospital
Nicola Nicolai - Istituto Nazionale dei Tumori, Milano, Italy
Soo-Hwang Teo - Subang Jaya Medical Centre
Lynn Greenhalgh - Boston Children's Hospital
Sara Strom - The University of Texas MD Anderson Cancer Center
Alex Henderson - Northern Genetics Service, Newcastle upon Tyne Hospitals, Newcastle upon Tyne, UK
John McGrath - Royal Devon and Exeter Hospital
David Gallagher - Mater Misericordiae University Hospital
Neil Aaronson - The Netherlands Cancer Institute
Audrey Ardern-Jones - Royal Marsden NHS Foundation Trust
Chris Bangma - Erasmus University Rotterdam
David Dearnaley - Royal Marsden NHS Foundation Trust
Philandra Costello - Princess Anne Hospital
Jorunn Eyfjord - RMIT University
Jeanette Rothwell - University of Manchester
Alison Falconer - Imperial College Healthcare NHS Trust
Henrik Gronberg - Umeå University
Freddie C. Hamdy - University of Oxford
Oskar Johannsson - Reykjavík University
Vincent Khoo - Royal Marsden NHS Foundation Trust
Zsofia Kote-Jarai - TEAM
Jan Lubinski - Pomeranian Medical University
Ulrika Axcrona - Norwegian Radium Hospital, Oslo, Norway
Jane Melia - University of Cambridge
Joanne McKinley - Peter MacCallum Cancer Centre
Anita V. Mitra - University College London
Clare Moynihan - TEAM
Gad Rennert - Carmel Medical Center
Mohnish Suri - Nottingham City Hospital
Penny Wilson - BioZenix, Altrincham, Cheshire, UK
Emma Killick - Royal Marsden NHS Foundation Trust
Sue Moss - Queen Mary University of London
Rosalind A. Eeles - Royal Marsden NHS Foundation Trust
The IMPACT Collaborators
Christine June Jacobs - School of Health Sciences
Publication Details: European urology, Vol.66(3), pp.489-499
Publisher: Elsevier B.V
Number of pages: 11
Date published: 01/09/2014
Identifiers: 99928826302346
Academic Unit: School of Health Sciences
Language: English
Resource Type: Journal article

Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study

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