TY - JOUR
T1 - Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer
AU - Castro, Elena
AU - Goh, Chee
AU - Olmos, David
AU - Saunders, Ed
AU - Leongamornlert, Daniel
AU - Tymrakiewicz, Malgorzata
AU - Mahmud, Nadiya
AU - Dadaev, Tokhir
AU - Govindasami, Koveela
AU - Guy, Michelle
AU - Sawyer, Emma
AU - Wilkinson, Rosemary
AU - Ardern-Jones, Audrey
AU - Ellis, Steve
AU - Frost, Debra
AU - Peock, Susan
AU - Evans, D Gareth
AU - Tischkowitz, Marc
AU - Cole, Trevor
AU - Davidson, Rosemarie
AU - Eccles, Diana
AU - Brewer, Carole
AU - Douglas, Fiona
AU - Porteous, Mary E
AU - Donaldson, Alan
AU - Dorkins, Huw
AU - Izatt, Louise
AU - Cook, Jackie
AU - Hodgson, Shirley
AU - Kennedy, M John
AU - Side, Lucy E
AU - Eason, Jacqueline
AU - Murray, Alex
AU - Antoniou, Antonis C
AU - Easton, Douglas F
AU - Kote-Jarai, Zsofia
AU - Eeles, Rosalind
PY - 2013/5/10
Y1 - 2013/5/10
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Agents, Hormonal/therapeutic use
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - BRCA1 Protein/genetics
KW - BRCA2 Protein/genetics
KW - Brachytherapy
KW - Follow-Up Studies
KW - Genetic Predisposition to Disease
KW - Germ-Line Mutation
KW - Heterozygote
KW - Humans
KW - Kaplan-Meier Estimate
KW - Lymph Nodes/pathology
KW - Lymphatic Metastasis
KW - Male
KW - Middle Aged
KW - Neoplasm Grading
KW - Neoplasm Staging
KW - Nomograms
KW - Palliative Care/methods
KW - Phenotype
KW - Predictive Value of Tests
KW - Prognosis
KW - Proportional Hazards Models
KW - Prostatectomy
KW - Prostatic Neoplasms/genetics
KW - Radiotherapy, Adjuvant
KW - Retrospective Studies
KW - Risk Assessment
KW - Risk Factors
U2 - 10.1200/JCO.2012.43.1882
DO - 10.1200/JCO.2012.43.1882
M3 - Article
C2 - 23569316
SN - 0732-183X
VL - 31
SP - 1748
EP - 1757
JO - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
IS - 14
ER -
