BRCA2 mutation increases mortality rate in prostate cancer
Men with prostate cancer who are carriers of the BRCA2 gene mutation have significantly increased mortality rates.
The study identified 938 families with the BRCA2 mutation, of which 277 (29.5%) contained one or more cases of prostate cancer, with a total of 434 cases. Of these, 67 men were found to carry the familial BRCA2 mutation and 116 were probable mutation carriers. A comparison group of men with the BRCA1 mutation was also identified. Of 1,735 families, 316 contained one or more cases of prostate cancer (18.2%), with a total of 457 cases. Of these, 37 carried the BRCA1 mutation and 82 men were probable carriers. The average age at diagnosis was similar for the two groups.
Survival analysis was performed to establish the overall survival of BRCA2 carriers with prostate cancer and relative survival compared with BRCA1 carriers. The median survival time was 4.0 years for the BRCA2 group compared with 8.0 years for the BRCA1 group, and the risk of mortality was found to be 70% greater in cases from BRCA2 families compared with BRCA1 (HR 1.7, 95% CI 1.2-2.4; P=0.002). The five-year survival rate was 57% and 39% for those with the BRCA1 and BRCA2 mutation respectively, and 35% and 12% respectively were still alive after 15 years.
Men with the BRCA2 gene mutation are known to be at increased risk of pancreatic cancer and at approximately five times the risk of prostate cancer compared with the general population. As a result, men with this mutation are often advised to have annual PSA testing from the age of 40 years.
The basis for the aggressive behaviour of BRCA2-associated prostate cancer is not known. However, there is much interest in the role of targeted chemotherapy in these patients. Cytotoxic chemotherapy is not generally used in the early treatment of prostate cancer, but it is possible that the BRCA2 subgroup may benefit.
Narod SA, Neuhausen S, Vichodez G. Rapid progression of prostate cancer in men with a BRCA2 mutation. Br J Cancer 2008;99:371-4Reviewer
Dr Jonathan Rees
GPwSI Urology, Bristol