(Reaffirmed March 2020)
Committee on Genetics
This Practice Advisory was developed by the American College of Obstetricians and Gynecologists’ Committee on Genetics in collaboration with Christopher M. Zahn, MD, Britton Rink, MD, and Steven J. Ralston, MD, MPH.
This Practice Advisory has been endorsed by the American College of Medical Genetics and Genomics, National Society of Genetic Counselors, Nurse Practitioners in Women’s Health, and the Society for Gynecologic Oncology.
On 6 March 2018, The U. S. Food and Drug Administration (FDA) authorized the 23andMe, Inc., Personal Genome Service® Genetic Health Risk Report for BRCA1 and BRCA2 (Selected Variants) 1. This is the first direct-to-consumer test to report on BRCA1 and BRCA2 gene mutations. The test evaluates three specific gene mutations – 185delAG and 5382insC for BRCA1, and 6174delT for BRCA2. These mutations are most common in individuals of Ashkenazi Jewish descent; these mutations are present in approximately 2 – 2.6% of Ashkenazi Jewish women, and approximately 0.1 – 0.2% in other populations 1 2 3 4 5 6. This particular test only screens for these three mutations; there are more than 1,000 known BRCA mutations and dozens of other genes associated with hereditary breast and ovarian cancer.
The American College of Obstetricians and Gynecologists issued a media statement regarding the FDA’s authorization of this test on March 12, 2018, and the ACOG Committee Opinion No. 724, “Consumer Testing for Disease Risk”, summarizes issues related to direct-to-consumer genetic testing 7 8. ACOG discourages direct-to-consumer genetic testing. This same recommendation applies to the 23andMe BRCA1 and BRCA2 mutation testing, based on significant concerns related to testing in the absence of appropriate pre- and post-test counseling. The assessment of cancer risk includes the evaluation of a number of potential risk factors for cancer, including family history, personal medical history and the ascertainment of appropriate indications for genetic testing 9. Identifying the appropriate genetic test for each individual and interpreting genetic test results are complex processes. A patient should be counseled regarding the potential limitations, risks and benefits of the information before genetic tests are ordered. Post-test counseling regarding cancer risk and implications for subsequent care is also imperative. Counseling should also address cascade testing options for blood relatives of individuals who have been identified with specific genetic mutations 10.
One of the main concerns about this specific test for BRCA mutations is the lack of reassurance associated with a “negative” test result. Since the test only evaluates for the presence of three mutations within two genes, a negative test does not exclude the possibility of other mutations within the BRCA1 or BRCA2 genes or other genes known to be associated with hereditary breast and ovarian cancer syndromes. A negative test for three specific mutations may lead to false reassurance for an individual woman, and the potential that she will not obtain the appropriate evaluation and counseling to determine if she may be a candidate for additional testing using a more expanded panel or benefit from enhanced screening protocols.
The interpretation of “positive” or abnormal test results are similarly problematic. The interpretation of a positive test requires the context of family history and an assessment of other risk factors to accurately quantify personal risk. There is limited data to support population based genetic testing for hereditary breast and ovarian cancer in the absence of risk factors. The risk of breast and ovarian cancer in a woman who has a positive test result from these three mutations within the BRCA genes when performed outside of clinical recommendations and in the absence of a personal or family history is unknown 11. Therefore, we are limited in our ability to accurately counsel a patient with a positive result: it is not clear which risk reduction strategies or subsequent screening would be appropriate. It is not clear that this group of patients will benefit or be harmed by potential interventions such as risk-reducing medications or surgeries.
ACOG recommends that women should only pursue this type of genetic testing under the care of a provider with experience and expertise in cancer genetics (e.g. a medical geneticist, genetic counselor, oncologist with expertise in cancer genetics, obstetrician-gynecologist with expertise in cancer genetics, or other similarly-qualified professionals). Should a patient pursue direct-to-consumer testing and seek medical advice after the results are available, the FDA recommends confirmatory testing and genetic counseling. 1 Direct-to-consumer test results should NOT be used as the sole basis for counseling regarding cancer risk, and should NOT be the sole determinant of subsequent follow-up and consideration of risk-reducing strategies.