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

Bancroft, Elizabeth K., Page, Elizabeth C., Castro, Elena, Lilja, Hans, Vickers, Andrew, Sjoberg, Daniel, Assel, Melissa, Foster, Christopher S., Mitchell, Gillian, Drew, Kate, Maehle, Lovise, Axcrona, Karol, Evans, D. Gareth, Bulman, Barbara, Eccles, Diana, McBride, Donna, van Asperen, Christi, Vasen, Hans, Kiemeney, Lambertus A., Ringelberg, Janneke, Cybulski, Cezary, Wokolorczyk, Dominika, Selkirk, Christina, Hulick, Peter J., Bojesen, Anders, Skytte, Anne-Bine, Lam, Jimmy, Taylor, Louise, Oldenburg, Rogier, Cremers, Ruben, Verhaegh, Gerald, van Zelst-Stams, Wendy A., Oosterwijk, Jan C., Blanco, Ignacio, Salinas, Monica, Cook, Jackie, Rosario, Derek J., Buys, Saundra, Conner, Tom, Ausems, Margreet G., Ong, Kai-ren, Hoffman, Jonathan, Domchek, Susan, Powers, Jacquelyn, Teixeira, Manuel R., Maia, Sofia, Foulkes, William D., Taherian, Nassim, Ruijs, Marielle, Helderman-van den Enden, Apollonia T., Izatt, Louise, Davidson, Rosemarie, Adank, Muriel A., Walker, Lisa, Schmutzler, Rita, Tucker, Kathy, Kirk, Judy, Hodgson, Shirley, Harris, Marion, Douglas, Fiona, Lindeman, Geoffrey J., Zgajnar, Janez, Tischkowitz, Marc, Clowes, Virginia E., Susman, Rachel, Ramón y Cajal, Teresa, Patcher, Nicholas, Gadea, Neus, Spigelman, Allan, van Os, Theo, Liljegren, Annelie, Side, Lucy, Brewer, Carole, Brady, Angela F., Donaldson, Alan, Stefansdottir, Vigdis, Friedman, Eitan, Chen-Shtoyerman, Rakefet, Amor, David J., Copakova, Lucia, Barwell, Julian, Giri, Veda N., Murthy, Vedang, Nicolai, Nicola, Teo, Soo-Hwang, Greenhalgh, Lynn, Strom, Sara, Henderson, Alex, McGrath, John, Gallagher, David, Aaronson, Neil, Ardern-Jones, Audrey, Bangma, Chris, Dearnaley, David, Costello, Philandra, Eyfjord, Jorunn, Rothwell, Jeanette, Falconer, Alison, Gronberg, Henrik, Hamdy, Freddie C., Johannsson, Oskar, Khoo, Vincent, Kote-Jarai, Zsofia, Lubinski, Jan, Axcrona, Ulrika, Melia, Jane, McKinley, Joanne, Mitra, Anita V., Moynihan, Clare, Rennert, Gad, Suri, Mohnish, Wilson, Penny, Killick, Emma, Moss, Sue, Eeles, Rosalind A., The IMPACT Collaborators, Ward, Robyn, Susman, Rachel and McGaughran, Julie M. (2014) Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study. European Urology, 66 3: 489-499. doi:10.1016/j.eururo.2014.01.003

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Author Bancroft, Elizabeth K.
Page, Elizabeth C.
Castro, Elena
Lilja, Hans
Vickers, Andrew
Sjoberg, Daniel
Assel, Melissa
Foster, Christopher S.
Mitchell, Gillian
Drew, Kate
Maehle, Lovise
Axcrona, Karol
Evans, D. Gareth
Bulman, Barbara
Eccles, Diana
McBride, Donna
van Asperen, Christi
Vasen, Hans
Kiemeney, Lambertus A.
Ringelberg, Janneke
Cybulski, Cezary
Wokolorczyk, Dominika
Selkirk, Christina
Hulick, Peter J.
Bojesen, Anders
Skytte, Anne-Bine
Lam, Jimmy
Taylor, Louise
Oldenburg, Rogier
Cremers, Ruben
Verhaegh, Gerald
van Zelst-Stams, Wendy A.
Oosterwijk, Jan C.
Blanco, Ignacio
Salinas, Monica
Cook, Jackie
Rosario, Derek J.
Buys, Saundra
Conner, Tom
Ausems, Margreet G.
Ong, Kai-ren
Hoffman, Jonathan
Domchek, Susan
Powers, Jacquelyn
Teixeira, Manuel R.
Maia, Sofia
Foulkes, William D.
Taherian, Nassim
Ruijs, Marielle
Helderman-van den Enden, Apollonia T.
Izatt, Louise
Davidson, Rosemarie
Adank, Muriel A.
Walker, Lisa
Schmutzler, Rita
Tucker, Kathy
Kirk, Judy
Hodgson, Shirley
Harris, Marion
Douglas, Fiona
Lindeman, Geoffrey J.
Zgajnar, Janez
Tischkowitz, Marc
Clowes, Virginia E.
Susman, Rachel
Ramón y Cajal, Teresa
Patcher, Nicholas
Gadea, Neus
Spigelman, Allan
van Os, Theo
Liljegren, Annelie
Side, Lucy
Brewer, Carole
Brady, Angela F.
Donaldson, Alan
Stefansdottir, Vigdis
Friedman, Eitan
Chen-Shtoyerman, Rakefet
Amor, David J.
Copakova, Lucia
Barwell, Julian
Giri, Veda N.
Murthy, Vedang
Nicolai, Nicola
Teo, Soo-Hwang
Greenhalgh, Lynn
Strom, Sara
Henderson, Alex
McGrath, John
Gallagher, David
Aaronson, Neil
Ardern-Jones, Audrey
Bangma, Chris
Dearnaley, David
Costello, Philandra
Eyfjord, Jorunn
Rothwell, Jeanette
Falconer, Alison
Gronberg, Henrik
Hamdy, Freddie C.
Johannsson, Oskar
Khoo, Vincent
Kote-Jarai, Zsofia
Lubinski, Jan
Axcrona, Ulrika
Melia, Jane
McKinley, Joanne
Mitra, Anita V.
Moynihan, Clare
Rennert, Gad
Suri, Mohnish
Wilson, Penny
Killick, Emma
Moss, Sue
Eeles, Rosalind A.
The IMPACT Collaborators
Ward, Robyn
Susman, Rachel
McGaughran, Julie M.
Title Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study
Journal name European Urology   Check publisher's open access policy
ISSN 0302-2838
Publication date 2014-09
Sub-type Article (original research)
DOI 10.1016/j.eururo.2014.01.003
Open Access Status
Volume 66
Issue 3
Start page 489
End page 499
Total pages 11
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2015
Language eng
Subject 2748 Urology
Formatted 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.
Keyword BRCA1
Prostate cancer
Prostate-specific antigen
Targeted screening
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
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School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 32 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 37 times in Scopus Article | Citations
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Created: Mon, 16 Feb 2015, 09:05:13 EST by Jon Swabey on behalf of Office of Deputy Vice-Chancellor (Research)