Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study

2.50
Hdl Handle:
http://hdl.handle.net/11287/593883
Title:
Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study
Authors:
Bancroft, E. K.; Page, E. C.; Castro, E.; Lilja, H.; Vickers, A.; Sjoberg, D.; Assel, M.; Foster, C. S.; Mitchell, G.; Drew, K.; Maehle, L.; Johannsson, O.; Khoo, V.; Kote-Jarai, Z.; Lubinski, J.; Axcrona, U.; Melia, J.; McKinley, J.; Mitra, A. V.; Moynihan, C.; Rennert, G.; Axcrona, K.; Suri, M.; Wilson, P.; Killick, E.; Impact Collaborators; Moss, S.; Eeles, R. A.; Evans, D. G.; Bulman, B.; Eccles, D.; McBride, D.; van Asperen, C.; Vasen, H.; Kiemeney, L. A.; Ringelberg, J.; Cybulski, C.; Wokolorczyk, D.; Selkirk, C.; Hulick, P. J.; Bojesen, A.; Skytte, A. B.; Lam, J.; Taylor, L.; Oldenburg, R.; Cremers, R.; Verhaegh, G.; van Zelst-Stams, W. A.; Oosterwijk, J. C.; Blanco, I.; Salinas, M.; Cook, J.; Rosario, D. J.; Buys, S.; Conner, T.; Ausems, M. G.; Ong, K. R.; Hoffman, J.; Domchek, S.; Powers, J.; Teixeira, M. R.; Maia, S.; Foulkes, W. D.; Taherian, N.; Ruijs, M.; Helderman-van den Enden, A. T.; Izatt, L.; Davidson, R.; Adank, M. A.; Walker, L.; Schmutzler, R.; Tucker, K.; Kirk, J.; Hodgson, S.; Harris, M.; Douglas, F.; Lindeman, G. J.; Zgajnar, J.; Tischkowitz, M.; Clowes, V. E.; Susman, R.; Ramon y Cajal, T.; Patcher, N.; Gadea, N.; Spigelman, A.; van Os, T.; Liljegren, A.; Side, L.; Brewer, Carole; Brady, A. F.; Donaldson, A.; Stefansdottir, V.; Friedman, E.; Chen-Shtoyerman, R.; Amor, D. J.; Copakova, L.; Barwell, J.; Giri, V. N.; Murthy, V.; Nicolai, N.; Teo, S. H.; Greenhalgh, L.; Strom, S.; Henderson, A.; McGrath, John S; Gallagher, D.; Aaronson, N.; Ardern-Jones, Angus; Bangma, C.; Dearnaley, D.; Costello, P.; Eyfjord, J.; Rothwell, J.; Falconer, A.; Gronberg, H.; Hamdy, F. C.
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.
Citation:
Eur Urol. 2014 Sep;66(3):489-99. Erratum in: Eur Urol. 2015 Jun;67(6):e126.
Publisher:
Elsevier
Journal:
European urology
Issue Date:
1-Sep-2014
URI:
http://hdl.handle.net/11287/593883
DOI:
10.1016/j.eururo.2014.01.003
PubMed ID:
24484606
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0302-2838(14)00004-9
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1873-7560
Appears in Collections:
2014 RD&E publications; Clinical Genetics (Peninsula Genetics)

Full metadata record

DC FieldValue Language
dc.contributor.authorBancroft, E. K.en
dc.contributor.authorPage, E. C.en
dc.contributor.authorCastro, E.en
dc.contributor.authorLilja, H.en
dc.contributor.authorVickers, A.en
dc.contributor.authorSjoberg, D.en
dc.contributor.authorAssel, M.en
dc.contributor.authorFoster, C. S.en
dc.contributor.authorMitchell, G.en
dc.contributor.authorDrew, K.en
dc.contributor.authorMaehle, L.en
dc.contributor.authorJohannsson, O.en
dc.contributor.authorKhoo, V.en
dc.contributor.authorKote-Jarai, Z.en
dc.contributor.authorLubinski, J.en
dc.contributor.authorAxcrona, U.en
dc.contributor.authorMelia, J.en
dc.contributor.authorMcKinley, J.en
dc.contributor.authorMitra, A. V.en
dc.contributor.authorMoynihan, C.en
dc.contributor.authorRennert, G.en
dc.contributor.authorAxcrona, K.en
dc.contributor.authorSuri, M.en
dc.contributor.authorWilson, P.en
dc.contributor.authorKillick, E.en
dc.contributor.authorImpact Collaboratorsen
dc.contributor.authorMoss, S.en
dc.contributor.authorEeles, R. A.en
dc.contributor.authorEvans, D. G.en
dc.contributor.authorBulman, B.en
dc.contributor.authorEccles, D.en
dc.contributor.authorMcBride, D.en
dc.contributor.authorvan Asperen, C.en
dc.contributor.authorVasen, H.en
dc.contributor.authorKiemeney, L. A.en
dc.contributor.authorRingelberg, J.en
dc.contributor.authorCybulski, C.en
dc.contributor.authorWokolorczyk, D.en
dc.contributor.authorSelkirk, C.en
dc.contributor.authorHulick, P. J.en
dc.contributor.authorBojesen, A.en
dc.contributor.authorSkytte, A. B.en
dc.contributor.authorLam, J.en
dc.contributor.authorTaylor, L.en
dc.contributor.authorOldenburg, R.en
dc.contributor.authorCremers, R.en
dc.contributor.authorVerhaegh, G.en
dc.contributor.authorvan Zelst-Stams, W. A.en
dc.contributor.authorOosterwijk, J. C.en
dc.contributor.authorBlanco, I.en
dc.contributor.authorSalinas, M.en
dc.contributor.authorCook, J.en
dc.contributor.authorRosario, D. J.en
dc.contributor.authorBuys, S.en
dc.contributor.authorConner, T.en
dc.contributor.authorAusems, M. G.en
dc.contributor.authorOng, K. R.en
dc.contributor.authorHoffman, J.en
dc.contributor.authorDomchek, S.en
dc.contributor.authorPowers, J.en
dc.contributor.authorTeixeira, M. R.en
dc.contributor.authorMaia, S.en
dc.contributor.authorFoulkes, W. D.en
dc.contributor.authorTaherian, N.en
dc.contributor.authorRuijs, M.en
dc.contributor.authorHelderman-van den Enden, A. T.en
dc.contributor.authorIzatt, L.en
dc.contributor.authorDavidson, R.en
dc.contributor.authorAdank, M. A.en
dc.contributor.authorWalker, L.en
dc.contributor.authorSchmutzler, R.en
dc.contributor.authorTucker, K.en
dc.contributor.authorKirk, J.en
dc.contributor.authorHodgson, S.en
dc.contributor.authorHarris, M.en
dc.contributor.authorDouglas, F.en
dc.contributor.authorLindeman, G. J.en
dc.contributor.authorZgajnar, J.en
dc.contributor.authorTischkowitz, M.en
dc.contributor.authorClowes, V. E.en
dc.contributor.authorSusman, R.en
dc.contributor.authorRamon y Cajal, T.en
dc.contributor.authorPatcher, N.en
dc.contributor.authorGadea, N.en
dc.contributor.authorSpigelman, A.en
dc.contributor.authorvan Os, T.en
dc.contributor.authorLiljegren, A.en
dc.contributor.authorSide, L.en
dc.contributor.authorBrewer, Caroleen
dc.contributor.authorBrady, A. F.en
dc.contributor.authorDonaldson, A.en
dc.contributor.authorStefansdottir, V.en
dc.contributor.authorFriedman, E.en
dc.contributor.authorChen-Shtoyerman, R.en
dc.contributor.authorAmor, D. J.en
dc.contributor.authorCopakova, L.en
dc.contributor.authorBarwell, J.en
dc.contributor.authorGiri, V. N.en
dc.contributor.authorMurthy, V.en
dc.contributor.authorNicolai, N.en
dc.contributor.authorTeo, S. H.en
dc.contributor.authorGreenhalgh, L.en
dc.contributor.authorStrom, S.en
dc.contributor.authorHenderson, A.en
dc.contributor.authorMcGrath, John Sen
dc.contributor.authorGallagher, D.en
dc.contributor.authorAaronson, N.en
dc.contributor.authorArdern-Jones, Angusen
dc.contributor.authorBangma, C.en
dc.contributor.authorDearnaley, D.en
dc.contributor.authorCostello, P.en
dc.contributor.authorEyfjord, J.en
dc.contributor.authorRothwell, J.en
dc.contributor.authorFalconer, A.en
dc.contributor.authorGronberg, H.en
dc.contributor.authorHamdy, F. C.en
dc.date.accessioned2016-01-19T12:36:17Zen
dc.date.available2016-01-19T12:36:17Zen
dc.date.issued2014-09-01en
dc.identifier.citationEur Urol. 2014 Sep;66(3):489-99. Erratum in: Eur Urol. 2015 Jun;67(6):e126.en
dc.identifier.issn1873-7560en
dc.identifier.pmid24484606en
dc.identifier.doi10.1016/j.eururo.2014.01.003en
dc.identifier.urihttp://hdl.handle.net/11287/593883en
dc.description.abstractBACKGROUND: 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.en
dc.language.isoengen
dc.publisherElsevieren
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0302-2838(14)00004-9en
dc.titleTargeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT studyen
dc.typeJournal Articleen
dc.typeMulticenter Studyen
dc.typeResearch Support, N.I.H., Extramuralen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalEuropean urologyen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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