Author Insights: BRCA1 and BRCA2 Gene Mutations Associated With Improved Ovarian Cancer Survival

Paul D. P. Pharoah, BM BCh, PhD, from the University of Cambridge in England, and colleagues found that having an inherited mutation in the BRCA1 or BRCA2 gene is associated with improved survival in women with invasive epithelial ovarian cancer. (Image: Mark Pharoah)

Women with inherited mutations in the BRCA1 or BRCA2 genes have an increased risk of developing breast and ovarian cancer, although not all cases of breast and ovarian cancer are the result of mutations in these genes. Now researchers have new evidence that women with invasive epithelial ovarian cancer and mutations in the BRCA1 or BRCA2 genes are more likely than women with ovarian cancer associated with other mutated genes to survive at least 5 years.

The finding, appearing today in JAMA, may help physicians customize therapeutic options for treating ovarian cancer and could assist scientists planning future research into targeted therapies.

The pooled analysis of 26 observational studies involving 3879 women with ovarian cancer found 52% of women with a BRCA2 mutation were alive 5 years after diagnoses, as were 44% of women with a BRCA1 mutation. Only 36% of women without the mutations were alive after 5 years. The researchers noted that the survival advantage seen in women carrying a BRCA1 or BRCA2 mutation could be related to “intrinsic biological differences, their response to therapeutic agents, or both.”

Paul D. P. Pharoah, BM BCh, PhD, corresponding author from the University of Cambridge in England, discusses his team’s findings:

“We’re interested in how your genetic makeup might influence outcomes for the diagnosis of cancer in general. For this study, we asked the question, ‘Do inherited mutations affect survival in women with ovarian cancer?’ The results of a literature review were inconclusive, so we needed to get all the data together for a definitive answer—and now we have it. Our results are statistically robust: BRCA1 and BRCA2 mutations are some of the strongest prognostic factors for ovarian cancer.

“We can speculate a little bit about the biology. There’s some evidence that ovarian tumors with BRCA1 or BRCA2 deficiencies respond better to platinum-based chemotherapy, so it’s entirely plausible that these women are responding better to chemotherapy. But our data do not directly tell us that. For noncarriers of BRCA1 or BRCA2, if platinum therapy, which is the mainstay of ovarian cancer treatment, is not working well, we need to develop alternative, more effective treatment.

“Our findings tell us that people conducting [treatment] trials in ovarian cancer should routinely test for mutations [in BRCA1 or BRCA2] to see if women with these mutations respond differently to different treatments. And if you’re doing a clinical trial in ovarian cancer, you should be testing for these mutations up front and deciding whether you want to include carriers in the trial.”

Categories: Genetics, Oncology, Ovarian Cancer, Women's Health