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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 EK 1 , Page EC 2 , Castro E 3 , Lilja H 4 , Vickers A 5 , Sjoberg D 5 Show all authors , Assel M 5 , Foster CS 6 , Mitchell G 7 , Drew K 8 , Mæhle L 9 , Axcrona K 9 , Evans DG 10 , Bulman B 10 , Eccles D 11 , McBride D 11 , van Asperen C 12 , Vasen H 13 , Kiemeney LA 14 , Ringelberg J 13 , Cybulski C 15 , Wokolorczyk D 15 , Selkirk C 16 , Hulick PJ 17 , Bojesen A 18 , Skytte AB 18 , Lam J 19 , Taylor L 19 , Oldenburg R 20 , Cremers R 14 , Verhaegh G 14 , van Zelst-Stams WA 14 , Oosterwijk JC 21 , Blanco I 22 , Salinas M 22 , Cook J 23 , Rosario DJ 24 , Buys S 25 , Conner T 25 , Ausems MG 26 , Ong KR 27 , Hoffman J 27 , Domchek S 28 , Powers J 28 , Teixeira MR 29 , Maia S 30 , Foulkes WD 31 , Taherian N 31 , Ruijs M 32 , Helderman-van den Enden AT 33 , Izatt L 34 , Davidson R 35 , Adank MA 36 , Walker L 37 , Schmutzler R 38 , Tucker K 39 , Kirk J 40 , Hodgson S 41 , Harris M 42 , Douglas F 43 , Lindeman GJ 44 , Zgajnar J 45 , Tischkowitz M 46 , Clowes VE 46 , Susman R 47 , Ramón y Cajal T 48 , Patcher N 49 , Gadea N 50 , Spigelman A 51 , van Os T 52 , Liljegren A 53 , Side L 54 , Brewer C 55 , Brady AF 56 , Donaldson A 57 , Stefansdottir V 58 , Friedman E 59 , Chen-Shtoyerman R 60 , Amor DJ 61 , Copakova L 62 , Barwell J 63 , Giri VN 64 , Murthy V 65 , Nicolai N 66 , Teo SH 67 , Greenhalgh L 68 , Strom S 69 , Henderson A 43 , McGrath J 70 , Gallagher D 71 , Aaronson N 32 , Ardern-Jones A 72 , Bangma C 20 , Dearnaley D 1 , Costello P 11 , Eyfjord J 73 , Rothwell J 10 , Falconer A 74 , Gronberg H 75 , Hamdy FC 76 , Johannsson O 58 , Khoo V 72 , Kote-Jarai Z 2 , Lubinski J 15 , Axcrona U 9 , Melia J 77 , McKinley J 8 , Mitra AV 78 , Moynihan C 2 , Rennert G 79 , Suri M 80 , Wilson P 81 , Killick E 1 , IMPACT Collaborators , Moss S 82 , Eeles RA 83

Affiliations 

  • 1 Cancer Genetics Unit and Academic Urology Unit, Royal Marsden NHS Foundation Trust, London, UK; Oncogenetics Team, Institute of Cancer Research, London, UK
  • 2 Oncogenetics Team, Institute of Cancer Research, London, UK
  • 3 Oncogenetics Team, Institute of Cancer Research, London, UK; Spanish National Cancer Research Centre, Madrid, Spain
  • 4 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 Medicine, Lund University, Malmö, Sweden
  • 5 Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
  • 6 HCA Healthcare Laboratories, London, WC1E 6JA, UK
  • 7 Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia
  • 8 Familial Cancer Centre, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
  • 9 Norwegian Radium Hospital, Oslo, Norway
  • 10 Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  • 11 Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
  • 12 Leiden University Medical Center, Leiden, The Netherlands
  • 13 Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands
  • 14 Radboud University Medical Centre, Nijmegen, The Netherlands
  • 15 International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
  • 16 Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, USA
  • 17 Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, USA; Priztker School of Medicine, University of Chicago, Chicago, IL, USA
  • 18 Vejle Hospital, Vejle, Denmark
  • 19 Department of Urology, Repatriation General Hospital, Daw Park, South Australia, Australia
  • 20 Erasmus Medical Center, Rotterdam, The Netherlands
  • 21 University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  • 22 Hereditary Cancer Program, Catalonian Institute of Oncology, L'Hospitalet, Barcelona, Spain
  • 23 Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK
  • 24 Royal Hallamshire Hospital, Sheffield, UK
  • 25 Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
  • 26 Department of Medical Genetics, University Medical Centre Utrecht, The Netherlands
  • 27 Clinical Genetics Unit, Birmingham Women's Hospital, Birmingham, UK
  • 28 Basser Research Center, University of Pennsylvania, Philadelphia, PA, USA
  • 29 Genetics Department and Research Center, Portuguese Oncology Institute, Porto, Portugal; Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal
  • 30 Genetics Department and Research Center, Portuguese Oncology Institute, Porto, Portugal
  • 31 McGill Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada
  • 32 The Netherlands Cancer Institute, Amsterdam, The Netherlands
  • 33 Maastricht University Medical Center, Department of Clinical Genetics, Maastricht, The Netherlands
  • 34 South East Thames Genetics Service, London, UK, Guy's Hospital, London, UK
  • 35 Duncan Guthrie Institute of Medical Genetics, Yorkhill NHS Trust, Glasgow, UK
  • 36 VU University Medical Center, Amsterdam, The Netherlands
  • 37 Churchill Hospital, Headington, Oxford, UK
  • 38 Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany
  • 39 Hereditary Cancer Clinic, Prince of Wales Hospital, Randwick, New South Wales, Australia; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
  • 40 Familial Cancer Service, Westmead Hospital, Westmead, Sydney, New South Wales, Australia; Sydney Medical School (University of Sydney) at Westmead Millennium Institute, Sydney, NSW, Australia
  • 41 St. George's Hospital, Tooting, London, UK
  • 42 Familial Cancer Centre, Monash Health, Clayton, Victoria, Australia
  • 43 Northern Genetics Service, Newcastle upon Tyne Hospitals, Newcastle upon Tyne, UK
  • 44 Familial Cancer Centre, The Royal Melbourne Hospital, Parkville, Victoria, Australia; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia
  • 45 Institute of Oncology, Ljubljana, Slovenia
  • 46 Addenbrooke's Hospital, Cambridge, UK; The University of Cambridge, Cambridge, UK
  • 47 Genetic Health Queensland, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia
  • 48 Hospital de Sant Pau, Barcelona, Spain
  • 49 Genetic Services of WA, King Edward Memorial Hospital, Subiaco, WA, Australia; Department of Paediatrics, University of Western Australia, Perth, WA, Australia
  • 50 Hospital Vall d'Hebron, Barcelona, Spain
  • 51 Hunter Family Cancer Service, Waratah, New South Wales, Australia; University of New South Wales, St. Vincent's Clinical School, Darlinghurst, New South Wales, Australia; Hereditary Cancer Clinic, The Kinghorn Cancer Centre, St. Vincent's Hospital, Sydney, New South Wales, Australia
  • 52 Academic Medical Center, Amsterdam, The Netherlands
  • 53 Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden
  • 54 NE Thames Regional Genetics Service, Institute of Child Health, London, UK
  • 55 Peninsular Genetics, Derriford Hospital, Plymouth, UK; Royal Devon and Exeter Hospital, Exeter, UK
  • 56 North West Thames Regional Genetics Service, Kennedy-Galton Centre, North West London Hospitals NHS Trust, Harrow, UK
  • 57 St. Michael's Hospital, Bristol, UK
  • 58 Landspitali-the National University Hospital of Iceland, Reykjavik, Iceland
  • 59 Chaim Shema Medical Center, Tel-Hashomer, Israel
  • 60 The Genetic Institute, Kaplan Medical Center, Rehovot, Israel
  • 61 Murdoch Childrens Research Institute, Parkville, Victoria, Australia
  • 62 National Cancer Institute, Bratislava, Slovak Republic
  • 63 University of Leicester, Leicester, UK; University Hospitals Leicester, Leicester, UK
  • 64 Fox Chase Cancer Center, Philadelphia, PA, USA
  • 65 Tata Memorial Centre, Mumbai, India
  • 66 Istituto Nazionale dei Tumori, Milano, Italy
  • 67 Cancer Research Initiatives Foundation, Subang Jaya Medical Centre, Selangor, Darul Ehsan, Malaysia
  • 68 Clinical Genetics, Royal Liverpool Children's Hospital, Liverpool, UK
  • 69 The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
  • 70 Royal Devon and Exeter Hospital, Exeter, UK
  • 71 Mater Misericordiae University Hospital, Dublin, Ireland
  • 72 Cancer Genetics Unit and Academic Urology Unit, Royal Marsden NHS Foundation Trust, London, UK
  • 73 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland
  • 74 Imperial College Healthcare NHS Trust, London, London, UK
  • 75 University Hospital, Umea, Sweden
  • 76 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK; Churchill Hospital, Headington, Oxford, UK
  • 77 The University of Cambridge, Cambridge, UK
  • 78 Oncogenetics Team, Institute of Cancer Research, London, UK; University College London Hospitals NHS Foundation Trust, London, UK
  • 79 CHS National Cancer Control Center, Carmel Medical Center, Haifa, Israel
  • 80 Nottingham City Hospital, Nottingham, UK
  • 81 BioZenix, Altrincham, Cheshire, UK
  • 82 Queen Mary University of London, London, UK
  • 83 Oncogenetics Team, Institute of Cancer Research, London, UK; Cancer Genetics Unit and Academic Urology Unit, Royal Marsden NHS Foundation Trust, London, UK. Electronic address: [email protected]
Eur Urol, 2014 Sep;66(3):489-99.
PMID: 24484606 DOI: 10.1016/j.eururo.2014.01.003

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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