A novel DNA test system that assesses a person’s genetic predisposition for certain cancers – the first of its kind granted marketing authorization by the Food and Drug Administration – may become a valuable new public health tool.
The Common Hereditary Cancers Panel (Invitae) was approved late September following FDA review under the De Novo process, a regulatory pathway for new types of low- to moderate-risk devices.
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Validation of the prescription-only in vitro test was based on assessments of more than 9,000 clinical samples, which demonstrated accuracy of at least 99% for all tested variants in 47 genes known to be associated with an increased risk of developing certain cancers, including breast, ovarian, uterine, prostate, colorectal, gastric, pancreatic as well as melanoma.
How the test system works
Next-generation sequencing assesses germline human genomic DNA extracted from a single blood sample collected at the point of care, such as a doctor’s office, and is sent to a laboratory for analysis.
Specifically, the system aims to detect substitutions, small insertion and deletion alterations, and copy number variants in the panel of 47 targeted genes.
Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological health, explained in an FDA press release announcing the marketing authorization.
Clinical interpretation is based on evidence from the published literature, prediction programs, public databases, and Invitae’s own variants database, the FDA statement explained.
What the test can do
Not only can the Common Hereditary Cancer Panel identify genetic variants that increase an individual’s risk of certain cancers, the panel can also help identify potential cancer-related hereditary variants in patients already diagnosed with cancer.
The most clinically significant genes the test system can detect include BRCA1 and BRCA2, which have known associations with hereditary breast and ovarian cancer syndrome; Lynch syndrome–associated genes including MLH1, MSH2, MSH6, PMS2, and EPCAM; CDH1, which is largely associated with hereditary diffuse gastric cancer and lobular breast cancer; and STK11, which is associated with Peutz-Jeghers syndrome.
“Patients should speak with a health care professional, such as a genetic counselor, to discuss any personal/family history of cancer, as such information can be helpful in interpreting test results,” the FDA advised.
What the test can’t do
The test is not intended to identify or evaluate all known genes tied to a person’s potential predisposition for cancer. The test is also not intended for cancer screening or prenatal testing.
For these reasons, and because genetics are not the only factor associated with developing cancer, negative test results could lead to misunderstanding among some patients about their cancer risk.
“Results are intended to be interpreted within the context of additional laboratory results, family history, and clinical findings,” the company wrote in a statement.
Test safety
Risks associated with the test include the possibility of false positive and false negative results and the potential for people to misunderstand what the results mean about their risk for cancer.
A false sense of assurance after a false negative result might, for instance, lead patients to forgo recommended surveillance or clinical management, whereas false positive test results could lead to inappropriate decision-making and undesirable consequences.
“These risks are mitigated by the analytical performance validation, clinical validation, and appropriate labeling of this test,” the agency explained.
Along with the De Novo authorization, the FDA is establishing special controls to define requirements for these tests. For instance, accuracy must be 99% or higher for positive agreement and at least 99.9% for negative agreement with a validated, independent method.
Public health implications
The information gleaned from this tool can “help guide physicians to provide appropriate monitoring and potential therapy, based on discovered variants,” Dr. Shuren said.
The marketing authorization of Invitae’s test established a new regulatory category, which “means that subsequent devices of the same type with the same intended use may go through FDA’s 510(k) premarket process,” the FDA explained.
A version of this article first appeared on Medscape.com.