Effect of BRCA Mutations on the Length of Survival in Epithelial Ovarian Tumors
Abstract & Commentary
Synopsis: Survival of patients with ovarian cancer is affected by BRCA germline mutation, with BRCA1/BRCA2 carriers with ovarian cancer surviving longer than noncarriers.
Source: David BY, et al. J Clin Oncol. 2002;20: 462-466.
Ben david and associates report a study in which blood samples and specimens of ovarian tumors were obtained at the time of primary surgery as part of a nationwide case-control study of women with ovarian cancer in Israel. The 3 most common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed, and patients were followed for up to 5 years (range, 20-64 months). The report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months vs 37.8 months; 3-year survival, 65.8% vs 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. David et al concluded that their data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation—at least in the early years after diagnosis.
Comment by David M. Gershenson, MD
Currently, approximately 10% of ovarian cancers are hereditary and can be directly associated with BRCA1 or BRCA2 gene mutations. For women who are identified as being BRCA carriers, chemoprevention with oral contraceptives plus surveillance (with transvaginal sonography and serum CA 125) or prophylactic oophorectomy are the principal options for management. For women with BRCA gene mutations who develop epithelial ovarian cancer, most have advanced stage, high-grade serous tumors. Over the past few years, there has been a debate about the prognosis of patients with BRCA-associated ovarian cancer. In the initial report on this subject, David et al presented data indicating that women with BRCA-associated ovarian cancer have a better outcome than those without BRCA-associated ovarian cancer.1 Some methodologic flaws in this study, however, cast some doubt about the findings. A subsequent study from Memorial Sloan-Kettering Cancer Center confirmed these findings.2 Nevertheless, there remained significant skepticism within the oncology community about these findings. Preliminary studies from other groups, including the Israeli team, were not able to confirm these observations. But now, with this most recent report, the evidence supporting a better outcome for BRCA-associated ovarian cancer patients has been strengthened. Although several mechanisms responsible for this phenomenon have been suggested, the molecular characteristics of the BRCA genes are not yet well enough understood to explain it.
Dr. Gershenson is Professor and Deputy Chairman, Department of Gynecology, M.D. Anderson Cancer Center, Houston.
References
1. Rubin SC, et al. N Engl J Med. 1996;335:1413-1416.
2. Boyd J, et al. JAMA. 2000;283:2260-2265.
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