lunes, 24 de febrero de 2014

Targeted Prostate Cancer Screening in BRCA1 and BRC... [Eur Urol. 2014] - PubMed - NCBI

Targeted Prostate Cancer Screening in BRCA1 and BRC... [Eur Urol. 2014] - PubMed - NCBI



 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 EK1Page EC2Castro E3Lilja H4Vickers A5Sjoberg D5Assel M5Foster CS6Mitchell G7Drew K8Mæhle L9Axcrona K9Evans DG10Bulman B10Eccles D11McBride D11van Asperen C12Vasen H13Kiemeney LA14Ringelberg J13Cybulski C15Wokolorczyk D15Selkirk C16Hulick PJ17,Bojesen A18Skytte AB18Lam J19Taylor L19Oldenburg R20Cremers R14Verhaegh G14van Zelst-Stams WA14Oosterwijk JC21Blanco I22Salinas M22,Cook J23Rosario DJ24Buys S25Conner T25Ausems MG26Ong KR27Hoffman J27Domchek S28Powers J28Teixeira MR29Maia S30Foulkes WD31,Taherian N31Ruijs M32den Enden AT33Izatt L34Davidson R35Adank MA36Walker L37Schmutzler R38Tucker K39Kirk J40Hodgson S41Harris M42,Douglas F43Lindeman GJ44Zgajnar J45Tischkowitz M46Clowes VE46Susman R47Ramón Y Cajal T48Patcher N49Gadea N50Spigelman A51van Os T52Liljegren A53Side L54Brewer C55Brady AF56Donaldson A57Stefansdottir V58Friedman E59Chen-Shtoyerman R60Amor DJ61Copakova L62,Barwell J63Giri VN64Murthy V65Nicolai N66Teo SH67Greenhalgh L68Strom S69Henderson A43McGrath J70Gallagher D71Aaronson N32Ardern-Jones A72Bangma C20Dearnaley D1Costello P11Eyfjord J73Rothwell J10Falconer A74Gronberg H75Hamdy FC76Johannsson O58Khoo V72Kote-Jarai Z2Lubinski J15Axcrona U9Melia J77McKinley J8Mitra AV78Moynihan C2Rennert G79Suri M80Wilson P81Killick E1The IMPACT Collaborators,Moss S82Eeles 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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