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BRCA2 Gene Mutation Tied to Better Survival in Ovarian Ca


 

From the Annual Meeting of the American Association for Cancer Research

Major Finding: The 5-year survival was 36% in those with no BRCA mutation, 46% in those with the BRCA1 mutation, and 61% in those with the BRCA2 mutation, after adjustment for stage, grade, histology, and age at diagnosis.

Data Source: A large, multicenter study investigating the impact of germline BRCA1 and BRCA2 mutations in 3,531 women with invasive epithelial ovarian cancer.

Disclosures: Ms. Bolton said she had no relevant financial disclosures.

ORLANDO – Ovarian cancer patients with BRCA1 or BRCA2 gene mutations have better survival than do those with neither mutation, and those with the BRCA2 mutation have better survival than do those with the BRCA1 mutation, according to the findings of a large, multicenter study.

The findings confirm the results of several prior smaller studies showing a survival advantage in mutation carriers vs. nonmutation carriers, and they provide the first direct evidence that BRCA1 and BRCA2 mutations have differing effects on survival, Kelly L. Bolton reported.

She and her colleagues studied 3,531 women with invasive epithelial ovarian cancer who were enrolled in one of 24 studies in the United States, Europe, Israel, and Asia, and for whom survival data were available. Included were 1,178 women with BRCA1, 367 with BRCA2, and 1,986 who were BRCA-negative.

The 5-year survival was 36% in those with no mutation, 46% of those with the BRCA1 mutation, and 61% of those with the BRCA2 mutation, after adjustment for stage, grade, histology, and age at diagnosis, said Ms. Bolton, a predoctoral fellow at the National Cancer Institute.

The difference in survival between the BRCA1 mutation carriers and those with no mutation was modest (hazard ratio, 0.84), although not statistically significant. However, the difference between the BRCA2 mutation carriers and both the noncarriers and the BRCA1 mutation carriers (after adjustment for age at diagnosis) did reach statistical significance (HR, 0.57 and 0.69, respectively;. Even after the exclusion of all but high-grade, advanced-stage serous cases, the survival differences persisted, Ms. Bolton reported.

A possible explanation for the differences, based on in vitro work and some retrospective trials, may lie in patients' responses to chemotherapy; those with the BRCA2 mutation may have an improved response, but unidentified biological differences among BRCA1 carriers, BRCA2 carriers, and noncarriers could also be driving the association, she said.

The BRCA1 and BRCA2 mutation carriers in this study did not differ in regard to tumor stage, grade, or histology. Compared with noncarriers, however, BRCA1 carriers were younger and BRCA2 carriers were older at diagnosis.

Furthermore, compared with noncarriers, BRCA1 and BRCA2 carriers were more likely to present with advanced-stage disease, high-grade disease and serous disease (

“The findings don't have any immediate impact on clinical practice, but they do have important implications [for both] clinical prediction and also trial design, particularly for clinical trials,” Ms. Bolton said, noting that although germline mutations in the BRCA1 and BRCA2 genes are rare in the general population, they are present in 10%-15% of those with ovarian cancer.

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