A large-scale study has shown BRCA2 to be the first gene associated with prostate cancer prognosis. The finding, which comes from a collaboration between researchers at the Spanish National Cancer Research Centre, The Institute of Cancer Research, and The Royal Marsden NHS Foundation Trust could lead to improved personalized therapies for men with BRCA2 mutations.
BRCA2 is one of the most common mutations associated with breast cancer, Its role in the development of prostate cancer, illuminated by a study of more than 2,000 men, confirmed something that had only been hinted at before: the mutation is associated with developing the cancer as well as with increased risk of disease progression. A separate study in 2011 conducted by an Australian group suggested the gene’s potential importance as a prognostic marker. But the impact of that study was limited by its small sample size of 148 men and the use of genetic assays with low sensitivity.
In the new study, Spanish researchers found that BRCA1/2 mutations, typically associated with inherited breast and ovarian cancers, confer a more aggressive prostate cancer with a higher probability of distant metastasis. The BRCA2 mutation is associated with poor survival outcomes, and the investigators recommend this information should be considered when deciding a course of clinical care for patients carrying this mutation.
“Whilst the majority of patients with prostate cancer have an excellent prognosis, one of the biggest challenges we face in daily clinical practice is the difficulty of identifying those patients in which the illness can be fatal,” says David Olmos, head of the Prostate Cancer and Genitourinary Tumors Clinical Research Unit at the Spanish National Cancer Research Centre.
The aggressiveness of prostate cancer is variable; some tumors never progress or spread while others rapidly do and are eventually lethal. In the past five years, clusters of genes associated with various degrees of severity of prostate cancer have been identified, but their relevance to clinical outcome has yet to be determined.
Researchers behind the new study analyzed tumor features and clinical outcomes of 2,019 prostate cancer patients. Of the total, 18 men carried the BRCA1 mutation, 61 carried the BRCA2 mutation, and the majority 1,940, carried neither mutation. Everyone, men and women, have two BRCA1 and two BRCA2 genes.
To assess prognostic value of the mutation, the scientists compared the genetic mutation and other prognostic factors with overall survival, cause-specific overall survival, and metastasis-free survival. Survival was longer in non-carriers than in carriers, and five-year cause-specific survival and metastasis-free survival was longer in people who did not carry the mutation as well.
“The results of this study suggest the need for a paradigm shift in the clinical management of patients with prostate cancer who are carriers of mutations in the BRCA genes,” says Elena Castro, lead author of the article published in the Journal of Clinical Oncology. “Current treatment standards for these patients appear to be insufficient and there are no specific action guidelines.”
April 10, 2013
http://www.burrillreport.com/article-gene_mutation_could_direct_prostate_cancer_care.html