The US Food and Drug Administration (FDA) has authorized the use of a direct-to-consumer (DTC) test for BRCA1/2 mutations. While it is not the first DTC genetic test to enter the US marketplace, this is the first one to test specifically BRCA mutations.

The new test is the Personal Genome Service Genetic Health Risk (GHR) Report for BRCA1/BRCA2 (Selected Variants), from the company 23andMe.

However, the scope of the test is limited because it can test for only three genetic variants out of more than 1000 known BRCA mutations. The three genetic mutations covered by the test are the most common ones found in Ashkenazi (East European) Jews, but they are not the most common BRCA1/2 mutations found in the general population, the agency explains.

Therefore, while a positive test result will alert individuals to an increased cancer risk, a negative result can be falsely reassuring. Because it tests for only three mutations, a negative result does not rule out the possibility that an individual may be carrying other BRCA mutations that elevate cancer risk.

“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,” said Donald St. Pierre, acting director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, in a statement.

But he added that there are a lot of caveats. “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,” he explained.

Katie Watson, a spokesperson for 23andme, reiterated that the test does not include most of the BRCA1 and BRCA2 variants found in people who are not Ashkenazi Jews. Therefore, a “variant not detected” result is far less informative for people with no Ashkenazi Jewish ancestry.

However, a “variant detected” result is still informative for other populations, she pointed out. “The effect of BRCA1 and BRCA2 variants on a person’s risk of developing breast, ovarian, prostate, and other cancers is well understood in people of many different ethnicities,” Watson said. “So if a woman has one or more of these genetic variants but is not of Ashkenazi Jewish descent, she still has a greatly increased risk of developing breast and ovarian cancer.  And men of other ethnicities who have a variant still have an increased risk of developing male breast cancer and, in some cases, prostate cancer.”

About 1 in 40 people of Ashkenazi Jewish ancestry have a deleterious BRCA mutation compared with about 1 in 400 people in the general population. The three variants included in this test account for over 90% of these BRCA1 and BRCA2 variants found in the Ashkenazi Jewish population.

Watson emphasized that a negative test result (“no variants detected”) does not significantly reduce one’s cancer risk because other genetic and nongenetic factors not tested here still play a large role in overall risk for these cancers. “However, a positive result is very informative and may significantly increase one’s genetic risk for certain cancers, especially breast and ovarian cancer,” Watson told Medscape Medical News.

“But we also make it very clear that the 23andme test does not describe a person’s overall risk of developing breast, ovarian, or prostate cancer or test for all possible variants in the BRCA1 and BRCA2 genes. Most BRCA1 and BRCA2 variants linked to hereditary cancers are not included in this test or test for variants in other genes linked to hereditary cancers,” Watson added.

Ramping Up Genetic Counseling

The number of women seeking genetic testing for BRCA gene mutations has steadily increased over the past decade. According to one recent study, which examined private insurance claims for BRCA mutation testing between 2004 and 2014, testing increased from 24.3% to 61.5%.

But despite the more than twofold increase in testing, most women are not getting genetic counseling — even though guidelines stress its importance. A study conducted in 2015 found that among 3628 women who underwent comprehensive BRCA testing that was ordered by their physicians, only 36.8% of the women (n = 1334) reported receiving genetic counseling from a genetics professional. Patients of obstetricians and gynecologists had the lowest rates of referral (n = 130 women [12.3%]).

Company Also Sells Reports

Watson explained that the company does provide information on why a customer may wish to engage in genetic counseling and how to contact local genetic counselors, which can be found in reports on the company website. “We believe people should have the choice to access their genetic information, and that’s always been core to our mission,” she said. “If a customer decides to view these particular reports, they will be provided with information about resources that may be helpful, including support groups, genetic counseling, and how to discuss results with family.”

The BRCA1/BRCA2 report will be part of the broader 23andMe Health + Ancestry service that includes more than 75 reports on health, wellness, traits, and ancestry, Watson explained, and this service costs $199. “New and existing 23andMe Health + Ancestry Service customers who were genotyped on the company’s most recent platforms will have access to this report in the coming weeks,” she said. “There will be no additional cost for the BRCA report for new or existing customers.”

Watson also pointed out that their test has a high level of accuracy. “The analytical testing of our genotyping process and our ability to correctly identify each of the variants in these reports met predetermined accuracy thresholds, per the FDA review process,” she said. “As with our other FDA-reviewed reports, we again demonstrated greater than 99% concordance as compared to Sanger sequencing, which is considered the gold standard for analyzing DNA. It also showed greater than 99% reproducibility and repeatability.”

The FDA concurs — they have determined that the company provided sufficient data to show that the test is accurate and can provide reproducible results. “The company submitted data on user comprehension studies, using representative GHR test reports, that showed instructions and reports were generally easy to follow and understood by a consumer,” the agency said in a press release. “The test report provides information describing what the results might mean, how to interpret results and where additional information about the results may be found.”

Target Audience

Despite its limitations, DTC testing could be a convenient and low-cost option for individuals who do not meet the current criteria for BRCA screening or who find that there are too many restrictions and barriers. For example, while genetic counseling is recommended, some insurance companies are now requiring that women be advised by a certified genetic counselor or someone with similar training before a genetic test can be ordered. The American Congress of Obstetricians and Gynecologists has opposed this restriction, warning that it places an unnecessary burden on the patient and could limit access to care.

In addition, large studies conducted in Canada, Israel, and the United Kingdom have indicated that more than half of Ashkenazi women who carry the mutation do not qualify for genetic testing on the basis of family history. Most young women with breast cancer do not have a family history of breast or ovarian cancer or Ashkenazi Jewish ancestry and therefore would also be ineligible for BRCA mutation testing before a cancer diagnosis.