Direct-to-consumer BRCA testing: Can a reasonable decision still require caution?

On March 6, the U.S. Food and Drug Administration (FDA) authorized 23andMe to expand its direct-to-consumer (DTC) genetic test to include selected variants in BRCA1 and BRCA2, two genes linked to breast and other cancers.

Much of the news coverage has featured words like “caution” and “beware.” In some cases, this language is appropriate. Still, it doesn’t mean that the FDA made a bad decision, or that no one would benefit from this expanded test.

The FDA is a public health agency, so its focus is on what’s best for the population, not what’s best for each individual. Further, the FDA has a complex mission, which includes “protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices.” It also includes “advancing the public health by helping to speed innovations.” The FDA has to balance those two aspects of its mission.

So what is the likely public health impact of this particular innovation? And why is access to this genetic test raising red flags? Consider how test recipients might react to their results.

Some people will find out that they are at elevated risk of cancer via the 23andMe test, information that may encourage them to adopt a more vigilant approach to their health such as undergoing more frequent exams and better monitoring for signs of breast cancer.

This would be particularly beneficial for individuals who are ineligible for insurer-paid genetic counseling and more comprehensive testing because they don’t have a family history of breast or ovarian cancer or don’t know their history or ancestry.

Other people will receive a negative (normal) BRCA test result from 23andMe and may conclude they don’t have to worry about breast cancer, when in fact they are at average or elevated risk.

This is especially worrisome if some in this group have a concerning family history and should see a genetics professional. 23andMe provided its educational materials plus reassuring results from user comprehension studies – but educational strategies are seldom 100 percent effective.

The level of interest and concern about the addition of BRCA testing may say something about the special status of breast cancer. After all, BRCA testing is not the first DTC genetic risk factor test. Early last year, 23andMe testing expanded to include genetic risk factors for 10 conditions, including Parkinson’s disease and late-onset Alzheimer’s disease.

In its decision summary, the FDA noted that in the case of Parkinson’s, for example, the test “does not provide a definitive determination of a person’s overall risk” given the range of relevant non-genetic factors and non-covered genetic factors. Similar risks of consumer confusion exist.

For anyone considering purchasing the 23andMe test, some further points to consider:

• We all have the BRCA1 and BRCA2 genes – concerns exist because some of us have variants within those genes that are pathogenic, meaning they are associated with an increased risk of developing breast cancer and certain other cancers. The word “mutation” is often used to describe a pathogenic variant.
• The 23andMe test does not look at every known pathogenic variant in BRCA1 and BRCA2. It looks at three pathogenic variants that are most common in people of Ashkenazi (Eastern European) Jewish ancestry. Even for Ashkenazi Jews, these variants are present in only about 2 percent of women. That drops to 0.1 percent for other ancestry groups.
• Men can also be at higher risk of cancer, including breast cancer, due to having pathogenic variants in BRCA1 and BRCA2.
• We have only begun to catalog and classify all the variants in BRCA1 and BRCA2. Even a comprehensive BRCA1 and BRCA2 panel test performed by a reputable genetic testing laboratory cannot currently deliver a definitive determination of a particular person’s overall risk.
• Under the Affordable Care Act, insurance companies are required to pay for genetic counseling and clinical BRCA testing for women who meet certain criteria. Information on insurance aspects and more, is available from advocacy and education groups like FORCE (Facing Our Risk of Cancer Empowered).

In sum, it’s possible to label the FDA decision “reasonable” and describe people who might benefit while urging caution, especially for anyone with a family history of cancer.

While additional health knowledge can often benefit a consumer, the challenges posed by DTC genetic testing underscore the value of using the results to engage in prevention and treatment conversations with your physician and, in the case of positive results, a genetic counselor or other genetics professional.

-By Mary Anderlik Majumder, J.D., Ph.D., associate professor in the Center for Medical Ethics and Health Policy at Baylor College of Medicine