FDA Approves First Direct-to-Consumer Test for Breast Cancer Risk

Federal regulators approved the first direct-to-consumer test for the BRCA genes, which increase the risk of breast and ovarian cancer, the agency announced on Tuesday.

The test for the BRCA1 and BRCA2 genes, from 23andMe, uses a saliva sample. But it assesses only three of the more than 1,000 known BRCA1/2 mutations, raising concerns that women who are told they do not have any of those variants will be lulled into believing that, as a result, they do not have an elevated risk for breast and ovarian cancer.

The three specific BRCA1/BRCA2 breast cancer gene mutations are most common in people with Ashkenazi (Eastern European) Jewish ancestry, accounting for more than 90 percent of their risk of heritable breast and ovarian cancer. But even in this population only 2 percent of women carry any of these three so-called “founder” mutations, the FDA said. Women with one of the mutations have a 45 percent to 85 percent chance of developing breast cancer by age 70, 23andMe said.

But these three variants are not the most common BRCA1/BRCA2 mutations in the general population: No more than 0.1 percent of women with non-Ashkenazi ancestry carry the mutations. “A negative result does not rule out the possibility that an individual carries other BRCA mutations that increase cancer risk,” the FDA warned.

Test Limitations
The 23andMe test “is a step forward in the availability of DTC genetic tests,” Donald St. Pierre, acting director of the FDA’s Office of In Vitro Diagnostics and Radiological Health, said in a statement. “But it has a lot of caveats.”

The agency therefore warned that individuals and their physicians should not use the test results to make decisions about treatments, including prophylactic removal of the breasts or ovaries. That should be based on more extensive testing. Myriad Genetics, which developed the first BRCA1/2 tests, assesses DNA for thousands of variants; it has long warned that other tests, which came on the market after the Supreme Court threw out Myriad’s key BRCA patents, could mislead women.

In addition, most cases of breast cancer are not hereditary, from BRCA or other mutations, but “sporadic,” meaning they arise at random or from smoking, obesity, exposure to toxic chemicals, hormone use, and other environmental factors.

“At a minimum, 23andMe should be clear with people about what their test is and isn’t and present the information in a fair and balanced way that the average person can understand,” said Myriad spokesman Ron Rogers, who added that some customers might be uncomfortable about 23andMe’s selling of genetic information to third parties.

For women with Ashkenazi ancestry, the test “is not too bad as a screen,” said Robert Cook-Deegan of Arizona State University, a longtime scholar in the field of genomics ethics and law. “But for other groups with different founder mutations, and there are many, it won’t help much. There’s a big need for users to understand that nuance, which is not widely understood.”

Direct-to-Consumer Tests
The FDA’s decision was based on data from 23andMe showing that its test can accurately identify the three genetic variants in saliva samples. The privately held company also submitted studies showing that consumers understood the report it will send to customers on what the results might mean, how to interpret them, and where to find additional information.

“Being the first and only direct-to-consumer genetics company to receive FDA authorization to test for cancer risk without a prescription is a major milestone for 23andMe and for the consumer,” Anne Wojcicki, 23andMe CEO and co-founder, said in a statement. “We believe it’s important for consumers to have direct and affordable access to this potentially life-saving information. … This authorization is incredibly valuable for those who might not be aware of their Ashkenazi Jewish descent.”

She, too, emphasized that “our test does not account for all genetic variants that can cause a higher risk of cancer, and people should continue with their recommended cancer screenings.” Myriad, for instance, has identified some 20,000 BRCA1/2 variants.

The decision follows one last year in which the FDA gave 23andMe the go-ahead to sell DNA tests assessing customers’ risk of 10 diseases, including Parkinson’s and late-onset Alzheimer’s. Those were the first FDA-approved direct-to-consumer tests for genetic risk of any disease or condition, which the agency said could help people make lifestyle decisions. At the time, the FDA also warned that genetic risk for complex diseases is not a sure thing: People whose 23andMe test does not find genetic variants that increase the risk of a disease can still develop it, and people whose DNA test shows no disease-causing variants might not.

The BRCA test will be part of 23andme’s $199 Health + Ancestry test. Existing customers can opt to receive BRCA information for no additional cost, and as with the other disease-risk tests they as well as new customers must specifically choose to receive the information.

“My libertarian streak says this, properly understood, is a good thing that increases access,” said Cook-Deegan, “although I do worry about proliferation of commercial purveyors as the sources of information and keeping the data.”