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
Por:
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, Cajal, TRY, Spigelman, A, Teo, SH, Nicolai, N, Aaronson, N, Ardern-Jones, A, Bangma, C, Dearnaley, D, Eyfjord, J, Falconer, A, Gronberg, H, Hamdy, F, Johannsson, O, Khoo, V, Kote-Jarai, Z, Lilja, H, Lubinski, J, Melia, J, Moynihan, C, Peock, S, Rennert, G, Schroder, 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, Easton, DF, Eeles, RA
Publicada:
1 ene 2011
Resumen:
What's known on the subject? and What does the study add?
Scientists have found a number of genetic factors that increase prostate cancer risk, including heritable mutations in the genes BRCA1 and BRCA2. These mutations are not common but can have major impact, as a BRCA2 mutation increases risk by up to seven-fold while a BRCA1 mutation is thought to double risk in men under 65. The IMPACT study aims to determine whether targeted screening in men with a known BRCA1 or BRCA2 mutation would lead to earlier diagnosis of prostate cancers.
This data from the IMPACT study adds to the increasing evidence that BRCA mutation carriers develop more aggressive disease. Although these are early results, it appears that PSA screening is more accurate at predicting potentially aggressive prostate cancer among men at higher risk of the disease due to a genetic predisposition than general population screening. This study provides support for continued screening in men with genetic mutations.
OBJECTIVE
To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls), was established. This is the first multicentre screening study targeted at men with a known genetic predisposition to prostate cancer. A preliminary analysis of the data is reported.
PATIENTS AND METHODS
Men aged 40-69 years from families with BRCA1 or BRCA2 mutations were offered annual prostate specific antigen (PSA) testing, and those with PSA > 3 ng/mL, were offered a prostate biopsy. Controls were men age-matched (+/- 5 years) who were negative for the familial mutation.
RESULTS
In total, 300 men were recruited (205 mutation carriers; 89 BRCA1, 116 BRCA2 and 95 controls) over 33 months. At the baseline screen (year 1), 7.0% (21/300) underwent a prostate biopsy. Prostate cancer was diagnosed in ten individuals, a prevalence of 3.3%. The positive predictive value of PSA screening in this cohort was 47 center dot 6% (10/21). One prostate cancer was diagnosed at year 2. Of the 11 prostate cancers diagnosed, nine were in mutation carriers, two in controls, and eight were clinically significant.
CONCLUSIONS
The present study shows that the positive predictive value of PSA screening in BRCA mutation carriers is high and that screening detects clinically significant prostate cancer. These results support the rationale for continued screening in such men.
Filiaciones:
Mitra, AV:
Inst Canc Res, Sutton SM2 5NG, Surrey, England
Bancroft, EK:
Inst Canc Res, Sutton SM2 5NG, Surrey, England
Royal Marsden Hosp NHS Fdn Trust, Sutton, Surrey, England
Barbachano, Y:
Inst Canc Res, Sutton SM2 5NG, Surrey, England
Royal Marsden Hosp NHS Fdn Trust, Sutton, Surrey, England
Page, EC:
Inst Canc Res, Sutton SM2 5NG, Surrey, England
Foster, CS:
Royal Liverpool Univ Hosp, Liverpool, Merseyside, England
Jameson, C:
Royal Marsden Hosp NHS Fdn Trust, Sutton, Surrey, England
Mitchell, G:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Lindeman, GJ:
Royal Melbourne Hosp, Parkville, Vic 3050, Australia
Stapleton, A:
Repatriat Gen Hosp, Adelaide, SA, Australia
Suthers, G:
Univ Adelaide, Dept Paediat, Adelaide, SA 5005, Australia
Evans, DG:
St Marys Hosp, CMFT, Manchester M13 0JH, Lancs, England
Cruger, D:
Vejle Hosp, Dept Clin Genet, Vejle, Denmark
Blanco, I:
Catalonian Inst Oncol, Barcelona, Spain
Mercer, C:
Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England
Kirk, J:
Westmead Hosp, Sydney, NSW, Australia
Maehle, L:
Norwegian Radium Hosp, Oslo, Norway
Hodgson, S:
St George Hosp, London, England
Walker, L:
Churchill Hosp, Oxford OX3 7LJ, England
Izatt, L:
Guys Hosp, London SE1 9RT, England
Douglas, F:
Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England
Tucker, K:
Prince Wales Hosp, Sydney, NSW, Australia
Dorkins, H:
NW London Hosp NHS Trust, Kennedy Galton Ctr, NW Thames Reg Genet Serv, Harrow, Middx, England
Clowes, V:
Addenbrookes Hosp, Cambridge, England
Male, A:
Inst Child Hlth, NE Thames Reg Genet Serv, London, England
Donaldson, A:
St Michaels Hosp, Bristol, Avon, England
Brewer, C:
Royal Devon & Exeter Hosp, Exeter EX2 5DW, Devon, England
Doherty, R:
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia
Bulman, B:
St Marys Hosp, CMFT, Manchester M13 0JH, Lancs, England
Osther, PJ:
Fredericia & Kolding Hosp, Dept Urol, Fredericia, Denmark
Salinas, M:
Catalonian Inst Oncol, Barcelona, Spain
Eccles, D:
Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England
Axcrona, K:
Norwegian Radium Hosp, Oslo, Norway
Jobson, I:
Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England
Newcombe, B:
Addenbrookes Hosp, Cambridge, England
Cybulski, C:
Fredericia & Kolding Hosp, Dept Urol, Fredericia, Denmark
Rubinstein, WS:
NorthShore Univ HealthSyst, Ctr Med Genet, Evanston, IL USA
Buys, S:
Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA
Townshend, S:
King Edward Mem Hosp, Perth, WA, Australia
Friedman, E:
Chaim Shema Med Ctr, Tel Hashomer, Israel
Domchek, S:
Abramson Canc Ctr, Philadelphia, PA USA
Cajal, TRY:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Spigelman, A:
Hunter Genet, Newcastle, NSW, Australia
Univ New S Wales, St Vincents Clin Sch, Sydney, NSW, Australia
Teo, SH:
Canc Res Initiat Fdn, Subang Jaya Med Ctr, Selangor Darul Ehsan, Malaysia
Univ Malaya, Kuala Lumpur, Malaysia
Nicolai, N:
Ist Nazl Tumori, I-20133 Milan, Italy
Aaronson, N:
Netherlands Canc Inst, Amsterdam, Netherlands
Ardern-Jones, A:
Royal Marsden Hosp NHS Fdn Trust, Sutton, Surrey, England
Bangma, C:
Erasmus Univ, Med Ctr, Rotterdam, Netherlands
Dearnaley, D:
Inst Canc Res, Sutton SM2 5NG, Surrey, England
Royal Marsden Hosp NHS Fdn Trust, Sutton, Surrey, England
Eyfjord, J:
Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland
Falconer, A:
Imperial Coll Healthcare NHS Trust, London, England
Gronberg, H:
Univ Hosp, Umea, Sweden
Hamdy, F:
Univ Oxford, John Radcliffe Hosp, Oxford OX3 9DU, England
Johannsson, O:
Univ Hosp Iceland, Reykjavik, Iceland
Khoo, V:
Inst Canc Res, Sutton SM2 5NG, Surrey, England
Kote-Jarai, Z:
Inst Canc Res, Sutton SM2 5NG, Surrey, England
Lilja, H:
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA
Lubinski, J:
Pomeranian Med Univ, Int Hereditary Canc Ctr, Szczecin, Poland
Melia, J:
Inst Canc Res, Sutton SM2 5NG, Surrey, England
Moynihan, C:
Inst Canc Res, Sutton SM2 5NG, Surrey, England
Peock, S:
Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Strangeways Res Labs, Cambridge, England
Rennert, G:
CHS Natl Canc Control Ctr, Carmel Med Ctr, Haifa, Israel
Schroder, F:
Erasmus Univ, Med Ctr, Rotterdam, Netherlands
Sibley, P:
Siemens Healthcare Diagnost, Caernarfon, Gwynedd, Wales
Suri, M:
City Hosp Nottingham, Nottingham, England
Wilson, P:
BioZenix, Altrincham, Cheshire, England
Bignon, YJ:
Ctr Jean Perrin, Oncol Mol Lab, Clermont Ferrand, France
Strom, S:
Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA
Tischkowitz, M:
McGill Univ, Dept Oncol, McGill Program Canc Genet, Montreal, PQ, Canada
McGill Univ, Dept Human Genet, Montreal, PQ, Canada
Liljegren, A:
Karolinska Univ Hosp, Stockholm, Sweden
Karolinska Inst, Stockholm, Sweden
Ilencikova, D:
Natl Canc Inst, Bratislava, Slovakia
Abele, A:
Riga Stradins Univ, Hereditary Canc Inst, Riga, Latvia
Kyriacou, K:
Cyprus Inst Neurol & Genet, Nicosia, Cyprus
van Asperen, C:
Leiden Univ, Med Ctr K5 R, Leiden, Netherlands
Kiemeney, L:
Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands
Easton, DF:
Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Strangeways Res Labs, Cambridge, England
Eeles, RA:
Inst Canc Res, Sutton SM2 5NG, Surrey, England
Royal Marsden Hosp NHS Fdn Trust, Sutton, Surrey, England
Green Accepted
|