The University of Southampton
University of Southampton Institutional Repository

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

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
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
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 47·6% (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.

prostate cancer, brca1, brca2, psa, genetic predisposition
1464-4096
28-39
Mitra, Anita V.
dda5ffa5-fa8e-444d-9bdb-07fd1cfbb120
Bancroft, Elizabeth K.
192e818b-3694-4987-b466-b890669e28ca
Barbachano, Yolanda
2b868199-8938-4946-8889-361066c41c3c
Page, Elizabeth C.
d2084609-f4f3-4687-8af8-909554cd226d
Foster, C.S.
47060461-5eb1-4f56-be75-0914ac23e607
Jameson, C.
9dcc38ab-d563-440f-8504-70cb3aacd181
Mitchell, G.
8e2ff092-f0cd-4529-bd6b-6a58ba5c81f8
Lindeman, G.J.
8062e832-7ab2-4cb5-875f-8d1a2e1121cc
Stapleton, A.
f7f9d13c-f3dc-4279-abb0-4d3f646dfb8f
Suthers, G.
6c231b40-edea-4c56-bf09-91609f2b3bca
Evans, D.G.
b58c99fc-4da0-4d7e-b140-f22307befe5e
Cruger, D.
8806017a-86a4-457c-a378-4e1990f3a09f
Blanco, I.
afbcc414-51d7-454c-91ba-d736cf158276
Mercer, C.
5889a50a-0e0b-49cd-94d0-4184c5f303d0
Kirk, J.
ca8167cc-b07c-46a9-a8b5-6b4526e6f5c5
Maehle, L.
8ce6b053-f377-4dad-8e5c-5a996224ea15
Hodgson, S.
745600cf-b91f-4f39-9b5e-4f76989d268f
Walker, L.
99ada328-aeda-4264-8fc8-3154e2090265
Izatt, L.
5cabcdef-374a-4441-b571-9c7b1665b720
Douglas, F.
9dc3db90-827e-419d-86f1-48e22b6845ab
Tucker, K.
35d94230-1c92-4a46-944a-91be6cb9e818
Dorkins, H.
c5c983b7-709c-4580-b98c-771a57aa31f0
Clowes, V.
adecd22c-5fc0-4b45-a54b-9b3ead18bd4c
Male, A.
c88130a2-6225-4c0c-8caa-1c0a3c651830
Donaldson, A.
ea10ac5a-4f77-4ef5-91d5-7f32ea33db36
Brewer, C.
f50e5721-93d3-43ef-8cd2-572f238d04be
Doherty, R.
beb5503d-2436-4f6b-8505-27a0acad9bcd
Bulman, B.
346fbf03-b500-45ac-b33b-caa4be74b788
Osther, P.J.
ebd65e7c-5246-42a6-917e-eee17b0d7556
Salinas, M.
04155faf-731f-42be-9223-082bcb749ed1
Eccles, D.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Axcrona, K.
e9ef7011-f4dd-4083-ae13-6cb3db553ef9
Jobson, I.
fff81e9c-4835-4707-85c0-55c6f0c6822f
Newcombe, B.
143a2fe2-5af3-4d61-88e3-9fbbdf9feb30
Cybulski, C.
f63a16af-2625-4ae3-996e-44de1b34aa9a
Rubinstein, W.S.
7d9c2ab9-ec3d-4647-97ba-79a27996d0e0
Buys, S.
354d23d1-eb04-4801-9cf0-293827ec79dd
Townshend, S.
684c9f4e-f405-42bf-a61d-4917c1f58d9d
Friedman, E.
3d30ff62-bca2-4859-b60e-3acceb0a863b
Domchek, S.
87369b99-d655-4d3d-ba6e-4c71b9d8e0c9
Ramon y Cajal, T.
fb92c77c-dce3-4124-98d0-78d162a3c972
Spigelman, A.
4008918e-0c23-4d79-8fcc-c0cbdfea3245
Teo, S.H.
41b92500-cd7a-4244-913c-126166a79b5d
Nicolai, N.
0641a472-51b9-4c76-bcae-2050115c2dbc
Aaronson, N.
1456789c-19f5-4f29-ad07-4c9763fcda4b
Ardern-Jones, A.
615ce40c-596a-4b29-9578-13bf644aa3e0
Bangma, C.
0fbe4b89-b415-440d-8dca-d35a0493c8cb
Dearnaley, D.
fafa76bc-7af7-4dda-8980-1ca268baab0e
Eyfjord, J.
9f85ccd1-48ca-4e14-8a9a-2503fdb59b85
Falconer, A.
8475bd66-ac83-4dce-a745-4e8105c2eeec
The IMPACT Study Collaborators
Mitra, Anita V.
dda5ffa5-fa8e-444d-9bdb-07fd1cfbb120
Bancroft, Elizabeth K.
192e818b-3694-4987-b466-b890669e28ca
Barbachano, Yolanda
2b868199-8938-4946-8889-361066c41c3c
Page, Elizabeth C.
d2084609-f4f3-4687-8af8-909554cd226d
Foster, C.S.
47060461-5eb1-4f56-be75-0914ac23e607
Jameson, C.
9dcc38ab-d563-440f-8504-70cb3aacd181
Mitchell, G.
8e2ff092-f0cd-4529-bd6b-6a58ba5c81f8
Lindeman, G.J.
8062e832-7ab2-4cb5-875f-8d1a2e1121cc
Stapleton, A.
f7f9d13c-f3dc-4279-abb0-4d3f646dfb8f
Suthers, G.
6c231b40-edea-4c56-bf09-91609f2b3bca
Evans, D.G.
b58c99fc-4da0-4d7e-b140-f22307befe5e
Cruger, D.
8806017a-86a4-457c-a378-4e1990f3a09f
Blanco, I.
afbcc414-51d7-454c-91ba-d736cf158276
Mercer, C.
5889a50a-0e0b-49cd-94d0-4184c5f303d0
Kirk, J.
ca8167cc-b07c-46a9-a8b5-6b4526e6f5c5
Maehle, L.
8ce6b053-f377-4dad-8e5c-5a996224ea15
Hodgson, S.
745600cf-b91f-4f39-9b5e-4f76989d268f
Walker, L.
99ada328-aeda-4264-8fc8-3154e2090265
Izatt, L.
5cabcdef-374a-4441-b571-9c7b1665b720
Douglas, F.
9dc3db90-827e-419d-86f1-48e22b6845ab
Tucker, K.
35d94230-1c92-4a46-944a-91be6cb9e818
Dorkins, H.
c5c983b7-709c-4580-b98c-771a57aa31f0
Clowes, V.
adecd22c-5fc0-4b45-a54b-9b3ead18bd4c
Male, A.
c88130a2-6225-4c0c-8caa-1c0a3c651830
Donaldson, A.
ea10ac5a-4f77-4ef5-91d5-7f32ea33db36
Brewer, C.
f50e5721-93d3-43ef-8cd2-572f238d04be
Doherty, R.
beb5503d-2436-4f6b-8505-27a0acad9bcd
Bulman, B.
346fbf03-b500-45ac-b33b-caa4be74b788
Osther, P.J.
ebd65e7c-5246-42a6-917e-eee17b0d7556
Salinas, M.
04155faf-731f-42be-9223-082bcb749ed1
Eccles, D.
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Axcrona, K.
e9ef7011-f4dd-4083-ae13-6cb3db553ef9
Jobson, I.
fff81e9c-4835-4707-85c0-55c6f0c6822f
Newcombe, B.
143a2fe2-5af3-4d61-88e3-9fbbdf9feb30
Cybulski, C.
f63a16af-2625-4ae3-996e-44de1b34aa9a
Rubinstein, W.S.
7d9c2ab9-ec3d-4647-97ba-79a27996d0e0
Buys, S.
354d23d1-eb04-4801-9cf0-293827ec79dd
Townshend, S.
684c9f4e-f405-42bf-a61d-4917c1f58d9d
Friedman, E.
3d30ff62-bca2-4859-b60e-3acceb0a863b
Domchek, S.
87369b99-d655-4d3d-ba6e-4c71b9d8e0c9
Ramon y Cajal, T.
fb92c77c-dce3-4124-98d0-78d162a3c972
Spigelman, A.
4008918e-0c23-4d79-8fcc-c0cbdfea3245
Teo, S.H.
41b92500-cd7a-4244-913c-126166a79b5d
Nicolai, N.
0641a472-51b9-4c76-bcae-2050115c2dbc
Aaronson, N.
1456789c-19f5-4f29-ad07-4c9763fcda4b
Ardern-Jones, A.
615ce40c-596a-4b29-9578-13bf644aa3e0
Bangma, C.
0fbe4b89-b415-440d-8dca-d35a0493c8cb
Dearnaley, D.
fafa76bc-7af7-4dda-8980-1ca268baab0e
Eyfjord, J.
9f85ccd1-48ca-4e14-8a9a-2503fdb59b85
Falconer, A.
8475bd66-ac83-4dce-a745-4e8105c2eeec

Mitra, Anita V., Bancroft, Elizabeth K., Barbachano, Yolanda, Page, Elizabeth C., Foster, C.S., Jameson, C., Mitchell, G., Lindeman, G.J., Stapleton, A., Suthers, G., Evans, D.G., 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, P.J., Salinas, M., Eccles, D., Axcrona, K., Jobson, I., Newcombe, B., Cybulski, C., Rubinstein, W.S., Buys, S., Townshend, S., Friedman, E., Domchek, S., Ramon y Cajal, T., Spigelman, A., Teo, S.H., Nicolai, N., Aaronson, N., Ardern-Jones, A., Bangma, C., Dearnaley, D., Eyfjord, J. and Falconer, A. , The IMPACT Study Collaborators (2010) 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. BJU International, 107 (1), 28-39. (doi:10.1111/j.1464-410X.2010.09648.x). (PMID:20840664)

Record type: Article

Abstract

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 47·6% (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.

This record has no associated files available for download.

More information

Published date: January 2010
Keywords: prostate cancer, brca1, brca2, psa, genetic predisposition

Identifiers

Local EPrints ID: 180171
URI: http://eprints.soton.ac.uk/id/eprint/180171
ISSN: 1464-4096
PURE UUID: 603b65cc-2099-4e23-8c93-a71cbaec120d
ORCID for D. Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 05 Apr 2011 13:37
Last modified: 15 Mar 2024 02:40

Export record

Altmetrics

Contributors

Author: Anita V. Mitra
Author: Elizabeth K. Bancroft
Author: Yolanda Barbachano
Author: Elizabeth C. Page
Author: C.S. Foster
Author: C. Jameson
Author: G. Mitchell
Author: G.J. Lindeman
Author: A. Stapleton
Author: G. Suthers
Author: D.G. Evans
Author: D. Cruger
Author: I. Blanco
Author: C. Mercer
Author: J. Kirk
Author: L. Maehle
Author: S. Hodgson
Author: L. Walker
Author: L. Izatt
Author: F. Douglas
Author: K. Tucker
Author: H. Dorkins
Author: V. Clowes
Author: A. Male
Author: A. Donaldson
Author: C. Brewer
Author: R. Doherty
Author: B. Bulman
Author: P.J. Osther
Author: M. Salinas
Author: D. Eccles ORCID iD
Author: K. Axcrona
Author: I. Jobson
Author: B. Newcombe
Author: C. Cybulski
Author: W.S. Rubinstein
Author: S. Buys
Author: S. Townshend
Author: E. Friedman
Author: S. Domchek
Author: T. Ramon y Cajal
Author: A. Spigelman
Author: S.H. Teo
Author: N. Nicolai
Author: N. Aaronson
Author: A. Ardern-Jones
Author: C. Bangma
Author: D. Dearnaley
Author: J. Eyfjord
Author: A. Falconer
Corporate Author: The IMPACT Study Collaborators

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×