BRCA Mutations Could Reduce 10-Year Survival by Up to 50 Percent
Carriers of BRCA gene mutations appear to be less responsive to conventional prostate cancer therapy
It has previously been reported that carriers of BRCA2 have over eight times the prostate cancer (PrCa) risk of non-carriers by age 65 (1), and for the first time last year, a link was made between PrCa prognosis and both BRCA1 and 2 mutation status (2). Now, a further study has cemented the link, and raised the questions: Should patients with PrCa be screened? And do they need different treatment approaches?
“We evaluated the role of germline BRCA mutations in PrCa in 2013, and demonstrated that they not only increase risk, but are associated with more aggressive disease,” (2) explains Elena Castro of the Spanish National Cancer Research Centre (CNIO), a senior author of both studies. “We showed that BRCA2 mutations are a prognostic factor for PrCa, independent of other classical factors, such as PSA levels at diagnosis, TMN, and Gleason score. In our second paper, we wanted to study the response of carriers to conventional treatments for localized cancer – radical prostatectomy zand external radiation therapy,” (3).
This second, more in-depth study involving over 1,300 patients (67 of which had mutations) demonstrated that carriers may have very different reactions to treatment. In patients who received radiotherapy, 10-year survival was less than half that of non-carriers (39 versus 80 percent). “The poor response to radiotherapy in BRCA carriers may be due to either radio-resistance or to the development of new primary tumors,” explains Castro. For surgery, the difference in 10-year survival was less pronounced, though still large; 67 percent for carriers and 91 percent for non-carriers
(Table 1).
| 3-Year Survival | 5-Year Survival | 10-Year Survival | |
| Non-carriers Surgery | 99% | 97% | 91% |
| Carriers Surgery | 96% | 89% | 67% |
| Non-carriers Radiotherapy | 96% | 91% | 80% |
| Carriers Radiotherapy | 85% | 57% | 39% |
The results of the two studies make it clear that more research is needed into the link between BRCA mutations and PrCa, and the resulting impact on prognosis. Further, only inherited mutations have been investigated so far: “Germline mutations occur in less than 2 percent of sporadic PrCa, but somatic BRCA2 losses have been described in approximately 15 percent of cases. There is currently no indication for genetic screening, but as technologies evolve and the cost of genome sequencing continues to decrease, it may prove cost-effective,” says Castro.
Screening could also lead to more tailored treatments. “Our results support close monitoring of BRCA mutation carriers following conventional treatment, as these patients tend to present with metastatic relapse earlier and more often than non-carriers,” adds Castro. “The most appropriate management of PrCa in this population is still unknown, but PARP (poly-ADP ribose polymerase) inhibitors may be a potential approach, and these patients may benefit from taking part in clinical trials.”
The team is now working on the molecular characterization of BRCA-mutated tumors to try and figure out why they are more aggressive and what treatments might best benefit patients who may not respond well to more traditional approaches.
- Z. Kote-Jarai et al., “BRCA2 is a Moderate Penetrance Gene Contributing to Young-Onset Prostate Cancer: Implications for Genetic Testing in Prostate Cancer Patients”, Br. J. Cancer, 105, 1230–1234 (2011).
- E. Castro et al., “Germline BRCA Mutations are Associated with Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer”, J. Clin. Oncol., 31, 1748–1757 (2013).
- E. Castro et al., “Effect of BRCA mutations on Metastatic Relapse and Cause-Specific Survival After Radical Treatment for Localised Prostate Cancer”, Eu. Urol., [in press corrected proof] (2014).
I have an extensive academic background in the life sciences, having studied forensic biology and human medical genetics in my time at Strathclyde and Glasgow Universities. My research, data presentation and bioinformatics skills plus my ‘wet lab’ experience have been a superb grounding for my role as an Associate Editor at Texere Publishing. The job allows me to utilize my hard-learned academic skills and experience in my current position within an exciting and contemporary publishing company.
