Eur Urol. 2014 Jan 15. pii: S0302-2838(14)00004-9. doi: 10.1016/j.eururo.2014.01.003. [Epub ahead of print]
Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study.
Bancroft EK1, Page EC2, Castro E3, Lilja H4, Vickers A5, Sjoberg D5, Assel M5, Foster CS6, Mitchell G7, Drew K8, Mæhle L9, Axcrona K9, Evans DG10, Bulman B10, Eccles D11, McBride D11, van Asperen C12, Vasen H13, Kiemeney LA14, Ringelberg J13, Cybulski C15, Wokolorczyk D15, Selkirk C16, Hulick PJ17,Bojesen A18, Skytte AB18, Lam J19, Taylor L19, Oldenburg R20, Cremers R14, Verhaegh G14, van Zelst-Stams WA14, Oosterwijk JC21, Blanco I22, Salinas M22,Cook J23, Rosario DJ24, Buys S25, Conner T25, Ausems MG26, Ong KR27, Hoffman J27, Domchek S28, Powers J28, Teixeira MR29, Maia S30, Foulkes WD31,Taherian N31, Ruijs M32, den Enden AT33, Izatt L34, Davidson R35, Adank MA36, Walker L37, Schmutzler R38, Tucker K39, Kirk J40, Hodgson S41, Harris M42,Douglas F43, Lindeman GJ44, Zgajnar J45, Tischkowitz M46, Clowes VE46, Susman R47, Ramón Y Cajal T48, Patcher N49, Gadea N50, Spigelman A51, van Os T52, Liljegren A53, Side L54, Brewer C55, Brady AF56, Donaldson A57, Stefansdottir V58, Friedman E59, Chen-Shtoyerman R60, Amor DJ61, Copakova L62,Barwell J63, Giri VN64, Murthy V65, Nicolai N66, Teo SH67, Greenhalgh L68, Strom S69, Henderson A43, McGrath J70, Gallagher D71, Aaronson N32, Ardern-Jones A72, Bangma C20, Dearnaley D1, Costello P11, Eyfjord J73, Rothwell J10, Falconer A74, Gronberg H75, Hamdy FC76, Johannsson O58, Khoo V72, Kote-Jarai Z2, Lubinski J15, Axcrona U9, Melia J77, McKinley J8, Mitra AV78, Moynihan C2, Rennert G79, Suri M80, Wilson P81, Killick E1; The IMPACT Collaborators,Moss S82, Eeles RA83.
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 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.
Copyright © 2014 European Association of Urology. All rights reserved.
KEYWORDS:
BRCA1, BRCA2, Prostate cancer, Prostate-specific antigen, Targeted screening
- PMID:
- 24484606
- [PubMed - as supplied by publisher]
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