Routine BRCA Mutation Testing Urged in Ovarian Cancer

June 24, 2012

By Megan Brooks

NEW YORK (Reuters Health) Jun 21 - Findings from the Australian Ovarian Cancer Study Group support BRCA1 and BRCA2 gene mutation testing in all women with nonmucinous, ovarian carcinoma, regardless of family history.

"BRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials," the researchers reported online June 18th in the Journal of Clinical Oncology.

In a cohort of 1,001 women with invasive epithelial (nonmucinous) ovarian carcinoma, 14.1% had germ-line BRCA 1/2 mutations. This was true for 6.6% of serous cancer patients (high-grade serous, 22.6%).

"Importantly," say the researchers, 44% of women with BRCA 1/2 mutations did not report a significant family history of breast or ovarian cancer. "Triage for genetic testing on family cancer history alone can no longer be recommended," they conclude.

In line with other studies, patients carrying germ-line mutations had improved rates of progression-free and overall survival. In the relapse setting, patients carrying mutations more frequently responded to both platin- and nonplatin-based treatment regimens than mutation-negative patients, even if they had relapsed early after initial treatment.

Mutation-negative patients who responded to multiple cycles of platin-based treatment were more likely to carry somatic BRCA1/2 mutations, the researchers say.

Dr. Gillian Mitchell, co-lead author on the paper and Director of the Familial Cancer Center at Peter MacCallum Cancer Centre, East Melbourne, Victoria, told Reuters Health: "This research tells us a patient's BRCA mutation status will help direct what treatments she should receive, and may help predict how she will respond to those treatments. With these mutations much more common than we previously thought...we believe BRCA testing should now be offered to all women diagnosed with common ovarian cancers, regardless of their family history."

Unfortunately, the rate of referral for genetic counseling and testing among ovarian cancer patients is low, the investigators say. Even among women in their cohort with a potentially significant family history, only 38.7% had contact with a genetics clinic during their cancer journey.

In their opinion, "Identification of BRCA1/2 mutation-positive patients appears to be a lost opportunity, given clear evidence of effective preventative strategies for those patients, in contrast to limited progress in early detection of ovarian cancer, or improvements in treatment outcomes in advanced disease."

"Even when genetic testing is performed it usually occurs late in the course of a patient's disease trajectory," the authors write, "yet our study and others demonstrate that mutation-positive patients have different treatment responses and survival characteristics compared with mutation-negative patients. Collectively, these findings suggest a re-evaluation of the timing and coverage of BRCA1/2 testing of ovarian cancer patients," the investigators conclude.

The investigators also say their results "argue strongly for the need to stratify patients based on germ-line BRCA mutation status in all new cancer therapy trials."

Professor David Bowtell, co-lead author of the paper, Head of Peter Mac's Cancer Genomics Program and Chief Investigator of the Australian Ovarian Cancer Study (AOCS), told Reuters Health: "Our results confirm that when designing and operating ovarian cancer trials, researchers need to stratify women according to whether or not they carry a BRCA gene mutation."

He and his co-authors also point out, "If there is to be an expansion of routine BRCA testing to all patients with high-grade ovarian cancer, and its application brought forward into acute clinical management either during or shortly after primary systemic therapy chemotherapy, new streamlined approaches to delivery of genetic counseling and genetic testing will be required."


J Clin Oncol 2012.


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