Oct. 11 (Bloomberg) -- Ovarian cancer patients with a genetic mutation best known for its ties to breast cancer have a higher survival rate than those without the mutation, a study in the Journal of the American Medical Association found.
The unexpected results suggest investigators may have erred by lumping two genetic mutations known as BRCA1 and BRCA2 together in recent years for research, said lead author Da Yang, a post-doctoral fellow at the University of Texas MD Anderson Cancer Center in Houston. While both are linked to breast and ovarian cancer, only women with BRCA2 mutations in the ovarian tumors have higher survival rates, according to the study released today by the journal.
The findings may have implications for determining the prognosis of women battling ovarian cancer and future studies examining potential new treatments, Yang said. Both mutations interfere with efforts to repair DNA, which creates the unstable environment that allows cancer to emerge. BRCA2 mutations also make it harder for cancer cells to fix the damage done by chemotherapy, making the treatment more effective for a longer period, the study showed.
“People all thought these two genes were the same -- the same function, influenced the same pathway,” Yang said in a telephone interview. “We are showing there are clear and distinct patterns for patients with these two mutations, so there is different overall survival, progression-free survival and chemotherapy response.”
Sanofi, Abbott Laboratories, AstraZeneca Plc and rival companies developing drugs known as Parp inhibitors should note the results, Yang said. The medicines are designed to block enzymes the cancer cells use to repair DNA. Patients with BRCA2 mutations that already have trouble fixing damaged cells may reap greater benefit from treatment, while mixing patients with different mutations in studies may yield conflicting results.
Nearly 22,000 women in the U.S. are diagnosed with ovarian cancer each year, and 14,000 die from the disease, according to the American Cancer Society. Women who have a BRCA1 mutation have a 39 percent to 54 percent chance of developing ovarian cancer in their lifetimes, compared with an 11 percent to 23 percent risk for those with a BRCA2 mutation, previous studies show.
The study is a major advance in understanding how new treatments for ovarian cancer should be used, wrote Victor Grann and Ramon Parsons, from Columbia University Medical Center’s cancer center in an editorial accompanying the study. Better understanding the differences in DNA repair linked to the two mutations may lead to more targeted treatment, they wrote.
The researchers used genetic information gathered from 316 women with ovarian cancer that was part of the National Institutes of Health’s Cancer Genome Atlas project, and compared their DNA makeup to the course of the disease. After five years, 61 percent of the women with BRCA2 mutations were alive, compared with 25 percent of those without the mutation.
The women also responded better to chemotherapy, had the disease progress more slowly and were more likely to survive, the study found. BRCA1 mutations and other changes that squelched the gene’s activity had no impact on prognosis.
“Right now, the chemotherapy cisplatin is the first line treatment for all patients,” Yang said. “If we can know the BRCA1 and BRCA2 status of the patient, we can at least predict if they will survive longer,” he said. “In the near future, some patients may choose” treatment based on the results, he said.
--Editors: Andrew Pollack, Angela Zimm
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