Genetic testing as part of routine cancer care, an approach called mainstreamed genetic testing, or MGT, is a feasible way to test BRCA mutations in ovarian cancer patients, a new U.K. study reports.
For those who tested positive, a relevant proportion of patients accessed targeted treatment they wouldn’t otherwise be eligible to receive.
The study, “Mainstreamed genetic testing for women with ovarian cancer: first-year experience,” appeared in the Journal of Medical Genetics.
Ovarian cancer may be caused by gene mutations. Specifically, mutations in the BRCA1 and BRCA2 genes cause 5.8% to 24.8% of all ovarian cancer cases.
Until recently, genetic testing was only available to U.K. patients with a family history of breast or ovarian cancer, or those of Ashkenazi Jewish ancestry.
A review study showed that only five of 15 guidelines recommend testing regardless of family history, ancestry, or cancer histology. But up to 44% of BRCA mutation carriers do not have a significant family history. Finding out which ovarian cancer patients carry BRCA mutations is important to guide treatment decisions.
A recent regulatory decision included women with high-grade epithelial ovarian cancer and without a family history of disease in the group eligible for testing through MGT. However, there is still a lack of consensus regarding how BRCA testing should be provided to ovarian cancer patients.
Introduced in February 2015, the research team evaluated the results of the first year of MGT at University College London Hospital, a tertiary referral center in North London, England. By assessing clinical outcomes, researchers aimed to inform additional development of MGT.
A total of 122 patients with high-grade non-mucinous (without mucus) ovarian cancer underwent BRCA testing through MGT. Eighteen (14.8%) showed deleterious BRCA1/BRCA2 mutations — those that increase the susceptibility or predisposition to a certain disease.
Of note, four BRCA carriers would have been missed with the older criteria for genetic testing. The data also showed that 22% of patients referred to genetic testing had a variant of unknown significance (VUS), which is a gene variant with unknown association with disease.
“It is unclear how oncologists interpret VUS and/or use them for clinical management,” the scientists wrote. “The pathogenicity of a VUS should be reviewed periodically, as in time it may be reclassified as either deleterious or benign.”
Six of the BRCA carriers started taking PARP inhibitors after MGT or were included in a clinical trial of one of these compounds.
The unchanged clinical management in the remaining patients is largely due to timing, the investigators considered, as treatment with Lynparza is only available for patients with platinum-sensitive relapsed ovarian cancer after three or more lines of treatment, and the managed access program to Zejula was not available at the time of the analysis.
“Clarifying BRCA mutation status while patients are still on first-line or second-line chemotherapy would identify those who are eligible for PARP inhibitor therapies or trials in the future,” the researchers wrote.
“This evaluation demonstrates that MGT is a feasible way of providing BRCA testing to patients with ovarian cancer and led to 33% of mutation carriers accessing targeted therapies,” they added.
The researchers said that all eligible patients should be offered BRCA testing, including newly diagnosed women and those years from diagnosis.
Future research should explore the psychosocial experiences of ovarian cancer patients who undergo MGT, especially those who find out they are mutation carriers, the investigators said.
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