BRCA2 Mutation in Ovarian Cancer Tumors Associated With Longer Patient Survival

Women with high-grade ovarian cancer involving tumors with BRCA2 mutations live longer and have a better response to platinum-based chemotherapy, researchers at The University of Texas MD Anderson Cancer Center and the Institute for Systems Biology report in the Journal of the American Medical Association.

“BRCA2-mutated tumors are more vulnerable to these DNA-damaging agents, which is really exciting because there are a number of drugs in clinical trials now that block DNA repair that might prove effective against these tumors in combinations,” said senior author Wei Zhang, PhD, professor in MD Anderson’s Department of Pathology.

The team’s in-depth research was based on a study published by The Cancer Genome Atlas (TCGA) of 489 high-grade serous ovarian cancer cases, the most common form of the disease. The study combined a thorough analysis of each tumor’s genome with complete clinical data on each patient.

Tumors were similar in grade and stage for all 316 ovarian cancer cases in the study by Zhang and colleagues. However, BRCA2 mutations were present in 29 tumors, and BRCA1 mutations were seen in 37 tumors.

Findings include:

• Of those patients with BRCA2 mutations in their tumors, 61% survived for 5 years, compared with 25% of patients with normal BRCA2 in their tumors
• After surgery and platinum treatment, 44% of those with BRCA2 mutations lived 3 years without disease progression, compared with 16% of those with normal BRCA2
• Survival was not associated with tumors involving BRCA1 mutations
• All patients with BRCA2 mutations responded to platinum chemotherapy, compared to 82% of patients with the normal gene and 80% of those with BRCA1 mutations in their tumors
• Response to platinum chemotherapy lasted 18 months for patients with BRCA2 mutations, compared with 11.7 months for patients normal BRCA2 and 12.5 months for those with BRCA1 mutations

“Uncovering the separate potential effects of BRCA1 and BRCA2 mutations takes us a step towards a more personalized approach to treating ovarian cancer, and perhaps other cancers,” Zhang said.

Source: The University of Texas MD Anderson Cancer Center.