Conventional therapies are less effective in prostate cancer with BRCA mutations
Prostate cancer patients with hereditary mutations in the BRCA genes do not respond as well to conventional treatment such as surgery and radiotherapy, and they have a lower survival rate than patients who do not have these genetic mutations. A study from Spain highlights the need for new clinical trials targeting BRCA mutations so treatment for these patients can be individualized.
Prostate cancer is the second most common form of cancer affecting men in the world. Approximately 2% of men with prostate cancer have hereditary BRCA mutations, and 12% of patients have sporadic mutations in the same genes.
A 2013 study showed that men with inherited mutations in the BRCA genes suffered from more aggressive tumors and died earlier. "That was when we found the first genetic factor associated with prostate cancer prognosis," explained Elena Castro, MD, PhD, of the Spanish National Cancer Research Center (CNIO), in Madrid, Spain.
More than 1,300 men participated in the study; 67 men had BRCA mutations. Men with BRCA mutations who had undergone radiotherapy had 10-year survival rates of 39%, compared to 80% for those without the genetic mutation. The difference in 10-year survival rates was less pronounced in men who have undergone surgery (67% for men with the BRCA gene and 91% for men without the BRCA mutation).
The smaller difference in survival rates between carriers and noncarriers who have undergone surgery shows that "these patients may require more long-term monitoring to establish whether or not this difference is significant," said Castro.
Smaller, less aggressive tumors are removed surgically while larger, more aggressive tumors are treated with surgery and radiation therapy. The prognostic factors that would help individualize treatment are unknown. The team's objective is to identify those patients with the least favorable prognosis, then select treatments that are the best match for the person's genetic characteristics.
PARP inhibitors target tumor cells with BRCA mutations. These molecules are very effective in the treatment of breast and ovarian cancers with BRCA mutations. PARP inhibitors are currently in clinical trials for the treatment of prostate cancer.
"Prostate tumors with sporadic mutations [present only in the tumor, not inherited] in BRCA, also respond to these inhibitors, according to recent data presented during the ESMO [European Society for European Oncology] 2014 Congress in Madrid," said David Olmos, MD, PhD, of the CNIO.
This study was published in the journal European Urology (2014; doi:10.1016/j.eururo.2014.10.022).