Update: FDA approves at-home test kits for inherited cancer: how useful are they?

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What is direct-to-consumer genetic testing?

With direct-to-consumer genetic testing, a person can order their own DNA test directly from the laboratory, with no doctor involved. In the past, testing for inherited mutations that raise the risk for disease has required a doctor's prescription. The FDA recently approved the first direct-to-consumer (DTC) test that looks for three mutations in the BRCA1 and BRCA2 genes. These mutations have been linked to increased risk for breast, ovarian, pancreatic, prostate and other cancers. This new approval allows people to order a kit, collect a saliva sample, send it directly to the 23andMe lab for testing, and receive their genetic results without involving a doctor.

What are the risks of the 23andMe direct-to-consumer genetic test? 

• The 23andMe test is an incomplete test for cancer risk.
  • The test only looks for 3 out of over 1000 possible mutations in BRCA genes (BRCA 185delAG, BRCA1 5382insC or BRCA2 6174delT). These three mutations are found most commonly in people of Ashkenazi (Eastern European) Jewish descent. For people who test positive for a mutation, the 23andMe test provides important information about their risk for cancer. But for people who test negative, the test does not provide much information about cancer risk.
  • The FDA approval statement notes that 1,000 other BRCA mutations also increase cancer risk. Technically, this is accurate, but it is a dramatic understatement. To date, over 5,400 different BRCA mutations (2,549 in BRCA1 and 2,941 in BRCA2) that can increase cancer risk have been identified.
  • Over 25 other genes have been linked to increased risk for hereditary breast, ovarian and other cancers. Mutations in other genes, such as CHEK2, ATM and PALB2 and others also increase cancer risk. So, a person whose 23andMe test is negative for a mutation may still have a different mutation in BRCA1 or BRCA2 or another gene that significantly increases cancer risk. 
  • The FDA report fails to mention that more complete tests are available to help people understand their cancer risk. Tests are available that look for the thousands of other BRCA mutations as well as mutations in other genes which are not detected by the 23andMe test. The cost for these tests are often covered by insurance and low-cost options may be available.
  • Individuals who receive a negative test result from 23andMe may have a false sense of confidence about their cancer risk. As the FDA cautions: “The test should not be used as a substitute for seeing your doctor for cancer screenings or counseling on genetic and lifestyle factors that can increase or decrease cancer risk.” 
• Leading experts set guidelines for cancer care, working through an organization known as the National Comprehensive Cancer Network (NCCN). NCCN recommends that people consult with a genetics professional before and after genetic testing. By sidestepping the need for a prescription, DTC genetic testing falls below standard-of-care.

Who can benefit the most from this test?

People of Ashkenazi Jewish descent who have never had BRCA testing will have the most benefit from the 23andMe test. About 2% of all Ashkenazi Jewish people—regardless of personal or family history of cancer—will carry one of the 3 mutations in the 23andMe test.

However, even Ashkenazi Jewish people can have a mutation in one of the over 5,000 other BRCA mutations, or in another gene like CHEK2, ATM or PALB2.  One study showed that among Jewish women with breast cancer, 0.8% have other BRCA mutations and 3 to 4% carry a mutation in another breast cancer gene (see our prior XRAY Does expanded genetic testing benefit Jewish women diagnosed with breast cancer?) These mutations are not detected in the 23andMe test. Therefore, negative results among Ashkenazi Jewish individuals are not conclusive either.

This new 23andMe DTC test has very limited usefulness for the general population. The test may benefit those who are unaware of their Jewish ethnicity and who test positive for one of the 3 mutations.

Healthcare professionals are not involved in the new 23andMe test

In DTC testing no medical or genetic counseling is included. Test results are returned electronically with a written explanation. Further questions and discussion of follow-up testing or treatment options are not included. As the FDA notes, this test should not be used to make health care decisions: “Consumers and health care professionals should not use the test results to determine any treatments, including anti-hormone therapies and prophylactic removal of the breasts or ovaries. Such decisions require confirmatory testing and genetic counseling. The test also does not provide information on a person’s overall risk of developing any type of cancer. The use of the test carries significant risks if individuals use the test results without consulting a physician or genetic counselor.”

The FDA examined how the test is performed and assures people that the test is accurate and reliable. The agency also warns that people should understand what this test does and does not tell them. They caution that without an expert explaining the meaning of the test results, misunderstandings may occur. Many genetics experts agree and believe that genetic testing for health information is best done in the clinical setting in consultation with medical professionals.

FDA notes

In their approval, the FDA make the following notes about test results through 23andMe:

• Consumers and health care professionals should not use the test results to determine any treatments, including anti-hormone therapies and prophylactic removal of the breasts or ovaries. Such decisions require confirmatory testing and genetic counseling.
• The test also does not provide information on a person’s overall risk of developing any type of cancer. The use of the test carries significant risks if individuals use the test results without consulting a physician or genetic counselor.
• The test only detects three out of more than 1,000 known BRCA mutations (the three most common in people of Ashkenazi Jewish ancestry). This means a negative result does not rule out the possibility that an individual carries other BRCA mutations that increase cancer risk. All individuals, whether they are of Ashkenazi Jewish descent or not, may have other mutations in BRCA1 or BRCA2 genes, or other cancer-related gene mutations that are not detected by this test. For this reason, a negative test result could still mean that a person has an increased risk of cancer due to gene mutations. 

What does this mean for me?

The 23andMe test can check your DNA for three specific BRCA mutations. Negative results provide very limited information, and are likely to be confusing to a person who undergoes testing without speaking to a genetics expert. Even if you are of Ashkenazi Jewish decent, you may have a mutation in BRCA1, 2 or other genes that are not included in this test.

Positive results may provide valuable information about risk for certain cancers, and options for manging these risks. However, because this testing is done without medical oversight, people should be aware of these important considerations:

• Your health care provider will be aware of your result only if you share them.
• People with a positive results might have to pay additional costs (dependent on individual insurance coverage) for a second test to confirm the results of their 23andMe test. People who have testing with 23andMe should consult with a genetic counselor to understand their results. 23andMe does not provide follow-up testing.
• For most consumers, the actual benefit of this test will be through follow-up genetic counseling and follow-up visits with doctors. 

Posted 3/19/18

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References

U.S. Food and Drug Administration. FDA authorizes, with special controls, direct-to-consumer test that reports three mutations in the BRCA breast cancer. Published March 6, 2018.

Disclosure

FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.