|
News
BRCA Mutation Confers Survival Advantage in Ovarian Cancer
Zosia Chustecka
January 8, 2008 Although women with the BRCA mutation are more likely to get ovarian cancer, they appear to have better survival rates than women who do not, suggests a large Israeli study. The better survival rate has been suggested before in other studies, but this is the largest and longest to date.
The data, reported in the January 1 issue of the Journal of Clinical Oncology, "clearly suggest that BRCA mutation status is one of the most important prognostic factors in epithelial ovarian cancer, other than stage and extent of surgical debulking," comments Noah Kauff, MD, from Memorial Sloan-Kettering Cancer Center, in New York, in an accompanying editorial.
BRCA mutation status will need to be taken into account when stratifying patients in clinical trials, given the magnitude of the survival advantage, said Dr. Kauff. It might eventually also prove useful in tailoring individual treatment, he added.
The finding comes from the National Israeli Study of Ovarian Cancer, which involved 779 Jewish women. However, for the comparison of mutation status, the researchers focused on 605 women of Ashkenazi origin, of whom 213 had
BRCA1 or BRCA2 mutations (designated as carriers). They found that carrying the mutation conferred a significant survival advantage, decreasing the mortality rate by 28% during the study period (median follow-up was 6.2 years). The median survival for carriers of the mutation was 53.7 months, compared with 37.9 months for noncarriers (P = .002). The difference was particularly pronounced among women who were diagnosed at stages 3 or 4, for whom the 5-year survival rates were 38.1% for carriers and 24.5% for noncarriers (P < .001), and among women with poor grade (45.5% for carriers vs 31.5% for noncarriers; P < .001).
This study confirms that BRCA1 or BRCA2 mutations are associated with improved long-term survival in ovarian cancer patients of Ashkenazi origin, the researchers conclude. They note that 6 other studies have reported a statistically significantly better survival among carriers, although 6 futher studies found that the difference was not statistically significant.
The better survival in mutation carriers might result from biologic characteristics of hereditary tumors and/or from a better response to therapy, the researchers speculate. Previous research has suggested that tumors lacking the BRCA1 mutation might be more sensitive to cisplatinum and other drugs that cause double-strand breaks in the DNA and that they might be more sensitive to radiotherapy. Whatever the reason for the better survival in carriers, the finding might have practical implications, because tailoring a specific treatment regimen in carrier patients based on chemosensitivity tests might improve survival compared with noncarriers, the researchers comment.
Neither the researchers nor the editorialist have disclosed any relevant financial relationships.
J Clin Oncol. 2008: 26:20-25 Abstract, 9-10 Abstract.
|
