FDA Authorizes First Direct-to-Consumer Genetic Test for Cancer Risk

The U.S. Food and Drug Administration (FDA) granted marketing authorization to 23andMe (Mountain View, Calif.) for its Personal Genome Service Genetic Health Risk Report for BRCA1/BRCA2—genetic mutations known to be associated with higher risk of breast, ovarian, and prostate cancers. It is the first authorized direct-to-consumer (DTC) genetic test for cancer risk, but the FDA authorization came with special controls that require labeling to indicate the tests' limitations.

The test only assesses three of more than 1,000 known BRCA mutations, meaning that a negative test result does not rule out an increased cancer risk. The three mutations examined in the DTC test are most common in people of European Jewish descent; yet only represent a very small minority (2 percent) of hereditary cancer mutations even in this population. According to a National Cancer Institute study, these mutations rarely occur (0 percent to 0.1 percent) in other ethnic populations.

A Summary of 23andMe's Authorizations

February 2015: Authorization enabled the company to launch 40+ carrier status reports directly to customers.

April 2017: Granted the first authorization by the FDA to enable DTC genetic health risk reports. To date the company has launched nine reports conditions, including late-onset Alzheimer's disease, Parkinson's disease, celiac disease, and hereditary thrombophilia.

April 2018: Authorization marks the first DTC genetic test for cancer risk—three BRCA-related mutations.

In a blog post 23andMe CEO and cofounder Anne Wojcicki says that insurance coverage criteria limit BRCA testing opportunities. She calls this authorization "a major milestone for 23andMe, but more importantly, a significant step forward for consumers who want direct and affordable access to their health information."

The authorization marks the third received by the company in the past three years using the de novo premarket review pathway and marks a dramatic reversal by the FDA, which forced 23andMe to withdraw its DTC Personal Genome Service (PGS) from the market back in 2013. PGS provided health reports on 254 diseases and conditions, including for categories such as carrier status, health risks, and drug response, which according to the FDA had been marketed as a medical device without proper authorization.

The FDA said 23andMe provided "sufficient data" to show that the test is accurate (i.e., can correctly identify the three genetic variants in saliva samples with greater than 99 percent concordance to Sanger sequencing, according to the company) and can provide reproducible results (also greater than 99 percent, according to 23andMe). Additionally, the company submitted data on user comprehension studies, showing that instructions and results reports were generally easy to follow and understood by a consumer.

"This test provides information to certain individuals who may be at increased breast, ovarian, or prostate cancer risk and who might not otherwise get genetic screening, and is a step forward in the availability of DTC genetic tests. But it has a lot of caveats," said Donald St. Pierre, acting director of the FDA's Office of In Vitro Diagnostics and Radiological Health, in a statement. "While the detection of a BRCA mutation on this test does indicate an increased risk, only a small percentage of Americans carry one of these three mutations and most BRCA mutations that increase an individual's risk are not detected by this test."

The FDA further cautioned that consumers and health care professionals should not use 23andMe's test results for treatment decisions without "confirmatory testing and genetic counseling."

Despite the FDA's special controls, critics in the genetics and oncology communities spoke out. Calling the test "incomplete" the American College of Medical Genetics and Genomics issued a statement saying it "believes that a test result has maximal value when the information it provides is interpreted in the context of a particular individual as well as our current knowledge and understanding of the test's limitations." The National Society of Genetic Counselors also issued a statement critical of the authorization saying results "may be confusing or misleading without appropriate education" and highlighted the important role medical professionals play in personalizing testing strategies.

23and Me says that new and existing 23andMe Health + Ancestry Service customers that were already genotyped on the company's most recent platforms will have access to the BRCA report in the coming weeks. However, customers must specifically choose if and when they want to receive this information, the company said in a statement.

Takeaway: The FDA's recent authorization of 23andMe's DTC genetic test for cancer risk based on three BRCA-related mutations is controversial. It is being hailed as an expansion of access to DTC genetic testing by supporters and is being lamented by critics as "incomplete" and potentially confusing to consumers.