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Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer

Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer
Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer
PURPOSE: To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes.

PATIENTS AND METHODS: This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1).

RESULTS: PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ? 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup.

CONCLUSION: Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.
1527-7755
1748-1757
Castro, E.
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Goh, C.
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Olmos, D.
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Saunders, E.
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Leongamornlert, D.
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Tymrakiewicz, M.
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Mahmud, N.
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Dadaev, T.
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Govindasami, K.
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Guy, M.
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Sawyer, E.
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Wilkinson, R.
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Ardern-Jones, A.
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Ellis, S.
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Frost, D.
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Peock, S.
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Evans, D.G.
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Tischkowitz, M.
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Cole, T.
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Davidson, R.
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Eccles, D.
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Brewer, C.
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Douglas, F.
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Porteous, M.E.
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Donaldson, A.
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Dorkins, H.
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Izatt, L.
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Cook, J.
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Hodgson, S.
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Kennedy, M.J.
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Side, L.E.
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Eason, J.
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Murray, A.
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Antoniou, A.C.
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Easton, D.F.
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Kote-Jarai, Z.
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Eeles, R.
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Castro, E.
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Goh, C.
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Olmos, D.
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Saunders, E.
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Leongamornlert, D.
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Tymrakiewicz, M.
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Mahmud, N.
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Dadaev, T.
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Govindasami, K.
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Guy, M.
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Sawyer, E.
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Wilkinson, R.
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Ardern-Jones, A.
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Ellis, S.
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Frost, D.
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Peock, S.
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Evans, D.G.
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Tischkowitz, M.
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Cole, T.
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Davidson, R.
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Eccles, D.
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Dorkins, H.
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Kennedy, M.J.
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Side, L.E.
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Eason, J.
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Murray, A.
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Antoniou, A.C.
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Kote-Jarai, Z.
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Eeles, R.
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Castro, E., Goh, C. and Olmos, D. et al. (2013) Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. Journal of Clinical Oncology, 31 (14), 1748-1757. (PMID:23569316)

Record type: Article

Abstract

PURPOSE: To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes.

PATIENTS AND METHODS: This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1).

RESULTS: PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ? 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup.

CONCLUSION: Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.

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More information

e-pub ahead of print date: 8 April 2013
Published date: 10 May 2013
Organisations: Cancer Sciences

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Local EPrints ID: 383024
URI: https://eprints.soton.ac.uk/id/eprint/383024
ISSN: 1527-7755
PURE UUID: 347506f9-e1f9-40fe-a527-d9eeb7df6a39

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Date deposited: 19 Oct 2015 08:19
Last modified: 27 Oct 2017 10:45

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Contributors

Author: E. Castro
Author: C. Goh
Author: D. Olmos
Author: E. Saunders
Author: D. Leongamornlert
Author: M. Tymrakiewicz
Author: N. Mahmud
Author: T. Dadaev
Author: K. Govindasami
Author: M. Guy
Author: E. Sawyer
Author: R. Wilkinson
Author: A. Ardern-Jones
Author: S. Ellis
Author: D. Frost
Author: S. Peock
Author: D.G. Evans
Author: M. Tischkowitz
Author: T. Cole
Author: R. Davidson
Author: D. Eccles
Author: C. Brewer
Author: F. Douglas
Author: M.E. Porteous
Author: A. Donaldson
Author: H. Dorkins
Author: L. Izatt
Author: J. Cook
Author: S. Hodgson
Author: M.J. Kennedy
Author: L.E. Side
Author: J. Eason
Author: A. Murray
Author: A.C. Antoniou
Author: D.F. Easton
Author: Z. Kote-Jarai
Author: R. Eeles

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