From OncoLog, November-December 2011, Vol. 56, Nos. 11-12
BRCA2 Mutations in Ovarian Cancers Indicate High Rates of Survival and Treatment Response for Patients
Women with high-grade ovarian cancers that have BRCA2 gene mutations live longer and respond better to platinum-based chemotherapy than do patients without BRCA mutations, researchers from The University of Texas MD Anderson Cancer Center and the Institute for Systems Biology reported in the October 12 issue of the Journal of the American Medical Association.
BRCA2 and BRCA1 are tumor-suppressing genes involved in DNA repair; women with mutations of either gene are at increased risk for developing breast and/or ovarian cancer.
The researchers reviewed data from The Cancer Genome Atlas for 316 patients with high-grade serous ovarian cancer, the most common form of the disease. The data for each patient included a genetic survey of the surgically resected primary tumor and comprehensive clinical data.
Most patients in the study had stage III or IV disease and histological grade 2 or 3 tumors. BRCA2 mutations were found in 29 ovarian cancers and BRCA1 mutations in 37. All patients had undergone surgery followed by platinum-based chemotherapy.
Patients with BRCA2 mutations in their tumors had a significantly higher 5-year overall survival rate (61%) than did patients without BRCA mutations in their tumors (25%). The 3-year progression-free survival rate also was significantly higher for patients whose tumors had BRCA2 mutations (44%) than for those whose tumors did not have BRCA mutations (16%). BRCA1 mutations in tumors were not significantly associated with survival.
All patients whose ovarian cancers had BRCA2 mutations responded to platinum-based chemotherapy, compared with 82% of patients whose tumors did not have any BRCA mutation and 80% of patients whose tumors had BRCA1 mutations.
“BRCA2-mutated ovarian cancers are more vulnerable to DNA-damaging chemotherapy agents, which is really exciting because a number of drugs now in clinical trials block DNA repair and might prove effective against these tumors, especially in combinations,” said Wei Zhang, Ph.D., a professor in the Department of Pathology at MD Anderson and the report’s senior author.
The researchers also found that tumors with BRCA2 mutations had a median 84 mutations per tumor sample compared with 52 mutations per tumor sample for tumors without BRCA mutations. Dr. Zhang said additional studies of BRCA1 and BRCA2 mutations are needed to better understand and exploit these findings.
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