Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis

Abstract

Background:The germline BRCA2 mutation is associated with increased prostate cancer (PrCa) risk. We have assessed survival in young PrCa cases with a germline mutation in BRCA2 and investigated loss of heterozygosity at BRCA2 in their tumours.Methods:Two cohorts were compared: one was a group with young-onset PrCa, tested for germline BRCA2 mutations (6 of 263 cases had a germline BRAC2 mutation), and the second was a validation set consisting of a clinical set from Manchester of known BRCA2 mutuation carriers (15 cases) with PrCa. Survival data were compared with a control series of patients in a single clinic as determined by Kaplan–Meier estimates. Loss of heterozygosity was tested for in the DNA of tumour tissue of the young-onset group by typing four microsatellite markers that flanked the BRCA2 gene, followed by sequencing.Results:Median survival of all PrCa cases with a germline BRCA2 mutation was shorter at 4.8 years than was survival in controls at 8.5 years (P=0.002). Loss of heterozygosity was found in the majority of tumours of BRCA2 mutation carriers. Multivariate analysis confirmed that the poorer survival of PrCa in BRCA2 mutation carriers is associated with the germline BRCA2 mutation per se.Conclusion:BRCA2 germline mutation is an independent prognostic factor for survival in PrCa. Such patients should not be managed with active surveillance as they have more aggressive disease.

Prostate cancer screening characteristics in men with BRCA1/2 mutations attending a high-risk prevention clinic

“…18 Also similar to other reports, [12][13][14][15][16] our BRCA2 mutation carriers had a higher rate of aggressive and non-curable disease than in the BRCA1 mutation carrier and Family History groups.…”

“…12 Other similar studies corroborate these findings. [13][14][15][16] Until recently, reports on the screening outcomes of male BRCA1/2 carriers have been scarce and often limited to specific founder mutations studied in a select population. In 2005, our centre evaluated the utility of targeted screening for detecting prostate cancer in BRCA1/2 carriers.…”

“…Therefore, while cancer was not more frequent in the Mutation Carrier group it did appear to be more aggressive, which is consistent with previous studies. [12][13][14][15][16]18 …”

“…[11][12][13][14][15][16][21][22][23][24] This study sought to understand the screening characteristics, cancer detection, and treatment outcomes for mutation carriers as compared to men with a family history of prostate cancer to understand the most appropriate screening and treatment regimens for these high-risk patients.…”

The role of BRCA1 and BRCA2 in prostate cancer

“…None of them included patients with the Icelandic founder mutation. Edwards et al 88 compared overall survival (OS) after PCa diagnosis in a series of 21 BRCA2 mutation carriers and 1587 controls, 263 of which had tested negative for BRCA2 mutations. Carriers had a median OS of only 4.8 years compared with 8.5 years for the noncarriers.…”