Biomedical Info

Women with ovarian cancer who have a mutated form of the BRCA2 gene may be more likely to respond to standard chemotherapy and have better overall and progression-free

 

survival than women without the mutation, according to a new study published October 12 in JAMA. The findings also suggested that women with BRCA1mutations had better overall and progression-free survival than women whose tumors lacked the mutations, but these latter findings were not statistically significant.

 

To conduct the observational study, Dr. Da Yang of the University of Texas M. D. Anderson Cancer Center and his colleagues analyzed genomic and clinical data from the tumors of 316 women with high-grade serous ovarian cancer. The data were made available in 2009 and 2010 from the NCI-supported The Cancer Genome Atlas(TCGA) program. Most of the women in the study (219) had nonmutated forms of the BRCA1 and BRCA2 genes. Only 27 women had BRCA2 mutations, and 35 had BRCA1 mutations.

 

Overall, 61 percent of women with BRCA2 mutations were alive after 5 years compared with 25 percent of women with non-mutated BRCA1 and BRCA2 genes and 44 percent of women with BRCA1 mutations. All of the women with BRCA2 mutations responded to chemotherapy, whereas 85 percent of women with wild-type BRCA genes and 80 percent of women with BRCA1-mutations responded.

 

“Our observations provide evidence that BRCA1 and BRCA2 mutations are differentially associated with patient survival compared with [non-mutated] BRCA and that this difference may be a result of distinct response to platinum-based treatment and different associations with genome instability,” the study authors wrote. Because of the relatively small size of the study, they acknowledged, more research is needed to validate the findings.

 

The study results provide “a major advance” in the understanding of how to test new treatments in women with ovarian cancer, wrote Drs. Victor Grann and Ramon Parsons of the Columbia University Medical Center in an accompanying editorial. They cited, for example, clinical trials that could test PARP inhibitors in women with ovarian cancer to test whether patients with BRCA1 or BRCA2 mutations respond differently.

 

A larger, NCI-led study presented earlier this year at the American Association for Cancer Research annual meeting had similar findings, including improved overall survival in women with ovarian cancer whose tumors hadBRCA2 mutations.

 

Further reading: "Study Suggests How the BRCA1 Protein May Help Suppress Tumors"