Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study.
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AuthorsBancroft, Elizabeth K
Page, Elizabeth C
Foster, Christopher S
Mitra, Anita V
Eeles, Rosalind A
Evans, D Gareth
van Asperen, Christi
Kiemeney, Lambertus A
Hulick, Peter J
van Zelst-Stams, Wendy A
Oosterwijk, Jan C
Rosario, Derek J
Ausems, Margreet G
Teixeira, Manuel R
Foulkes, William D
Helderman-van den Enden, Apollonia T
Adank, Muriel A
Lindeman, Geoffrey J
Clowes, Virginia E
Ramón y Cajal, Teresa
van Os, Theo
Brady, Angela F
Amor, David J
Giri, Veda N
Hamdy, Freddie C
MetadataShow full item record
CitationEur. Urol. 2014, 66 (3):489-99
AbstractMen 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 enrollment 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 enrollment, 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.
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- Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers.
- Authors: Page EC, Bancroft EK, Brook MN, Assel M, Hassan Al Battat M, Thomas S, Taylor N, Chamberlain A, Pope J, Raghallaigh HN, Evans DG, Rothwell J, Maehle L, Grindedal EM, James P, Mascarenhas L, McKinley J, Side L, Thomas T, van Asperen C, Vasen H, Kiemeney LA, Ringelberg J, Jensen TD, Osther PJS, Helfand BT, Genova E, Oldenburg RA, Cybulski C, Wokolorczyk D, Ong KR, Huber C, Lam J, Taylor L, Salinas M, Feliubadaló L, Oosterwijk JC, van Zelst-Stams W, Cook J, Rosario DJ, Domchek S, Powers J, Buys S, O'Toole K, Ausems MGEM, Schmutzler RK, Rhiem K, Izatt L, Tripathi V, Teixeira MR, Cardoso M, Foulkes WD, Aprikian A, van Randeraad H, Davidson R, Longmuir M, Ruijs MWG, Helderman van den Enden ATJM, Adank M, Williams R, Andrews L, Murphy DG, Halliday D, Walker L, Liljegren A, Carlsson S, Azzabi A, Jobson I, Morton C, Shackleton K, Snape K, Hanson H, Harris M, Tischkowitz M, Taylor A, Kirk J, Susman R, Chen-Shtoyerman R, Spigelman A, Pachter N, Ahmed M, Ramon Y Cajal T, Zgajnar J, Brewer C, Gadea N, Brady AF, van Os T, Gallagher D, Johannsson O, Donaldson A, Barwell J, Nicolai N, Friedman E, Obeid E, Greenhalgh L, Murthy V, Copakova L, Saya S, McGrath J, Cooke P, Rønlund K, Richardson K, Henderson A, Teo SH, Arun B, Kast K, Dias A, Aaronson NK, Ardern-Jones A, Bangma CH, Castro E, Dearnaley D, Eccles DM, Tricker K, Eyfjord J, Falconer A, Foster C, Gronberg H, Hamdy FC, Stefansdottir V, Khoo V, Lindeman GJ, Lubinski J, Axcrona K, Mikropoulos C, Mitra A, Moynihan C, Rennert G, Suri M, Wilson P, Dudderidge T, IMPACT Study Collaborators., Offman J, Kote-Jarai Z, Vickers A, Lilja H, Eeles RA
- Issue date: 2019 Dec
- Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study.
- Authors: Mitra AV, Bancroft EK, Barbachano Y, Page EC, Foster CS, Jameson C, Mitchell G, Lindeman GJ, Stapleton A, Suthers G, Evans DG, Cruger D, Blanco I, Mercer C, Kirk J, Maehle L, Hodgson S, Walker L, Izatt L, Douglas F, Tucker K, Dorkins H, Clowes V, Male A, Donaldson A, Brewer C, Doherty R, Bulman B, Osther PJ, Salinas M, Eccles D, Axcrona K, Jobson I, Newcombe B, Cybulski C, Rubinstein WS, Buys S, Townshend S, Friedman E, Domchek S, Ramon Y Cajal T, Spigelman A, Teo SH, Nicolai N, Aaronson N, Ardern-Jones A, Bangma C, Dearnaley D, Eyfjord J, Falconer A, Grönberg H, Hamdy F, Johannsson O, Khoo V, Kote-Jarai Z, Lilja H, Lubinski J, Melia J, Moynihan C, Peock S, Rennert G, Schröder F, Sibley P, Suri M, Wilson P, Bignon YJ, Strom S, Tischkowitz M, Liljegren A, Ilencikova D, Abele A, Kyriacou K, van Asperen C, Kiemeney L, IMPACT Study Collaborators., Easton DF, Eeles RA
- Issue date: 2011 Jan
- Imaging-based prostate cancer screening among BRCA mutation carriers-results from the first round of screening.
- Authors: Segal N, Ber Y, Benjaminov O, Tamir S, Yakimov M, Kedar I, Rosenbaum E, Sela S, Ozalvo R, Shavit-Grievink L, Keder D, Baniel J, Margel D
- Issue date: 2020 Nov
- The role of the prostate cancer gene 3 urine test in addition to serum prostate-specific antigen level in prostate cancer screening among breast cancer, early-onset gene mutation carriers.
- Authors: Cremers RG, Eeles RA, Bancroft EK, Ringelberg-Borsboom J, Vasen HF, Van Asperen CJ, IMPACT Steering Committee., Schalken JA, Verhaegh GW, Kiemeney LA
- Issue date: 2015 May
- Male BRCA1 and BRCA2 mutation carriers: a pilot study investigating medical characteristics of patients participating in a prostate cancer prevention clinic.
- Authors: Horsburgh S, Matthew A, Bristow R, Trachtenberg J
- Issue date: 2005 Oct 1