Even for genetics experts, the decisions and communication around genetic testing for patients such as Anthony, Zoe, and Nicole (above) can be complicated.
Once it has been determined that genetic testing is indicated, it is important to select the test that will provide the most information for the patient and his or her family. These seven tips can inform your cancer risk assessment and genetic testing decision-making. Remember that you can always refer or consult with a cancer genetics expert if you have questions or need more help!
According to the USPSTF as well as numerous professional societies, cancer genetic testing is NOT currently recommended for the general population. For an average risk patient, cancer genetic testing is more likely to result in an ambiguous finding than a clinically significant mutation. For practice assessing risk and identifying candidates for genetic testing, see the free course Categorizing Cancer Risk.
Until the causative gene in the family has been identified, a negative result in an unaffected patient is not completely reassuring. Therefore, testing is usually most cost-effective for the family, and most informative for unaffected relatives, when it is first performed in a cancer-affected relative. If a pathogenic variant, or mutation, is identified in a cancer-affected relative, other at-risk family members can have targeted testing for that specific variant at lower cost. Practice selecting effective genetic tests in courses about breast cancer and colorectal cancer.
If a causative variant has been identified in the family, relatives should be tested for that variant alone. Each first-degree relative (children, parents, siblings) of the affected individual has a 50% chance of also having the variant. Each second-degree relative (aunts, uncles, grandparents) has a 25% chance of having the variant. By targeting testing to the known pathogenic variant, you can save time and money by identifying close relatives who need increased screening and those who do not. This testing strategy is also known as cascade screening.
Genetic testing will be appropriate for many, but not all, patients at high risk. The clinician and the family must decide together whether the benefits of testing justify the limitations and risks. Consultation or referral to a cancer genetics expert during the pre-test counseling and decision-making process can help to ensure the patient is informed about his or her options and understands the implications of different testing outcomes. To practice weighing the benefits and limitations of testing for a specific patient, see the free course Pre-test Decisions & Counseling.
While there are a few genes that account for the majority of hereditary cancers, the clinical presentation of the associated syndromes may overlap with each other. In these cases, testing of more than one gene may be indicated. As the cost of genetic testing declines and the scope of testing technology expands, multi-gene panels are increasingly a cost-effective option. However, the risk for uncertain results and incidental findings increases with the number of genes included in the test, so this must be weighed against the increased sensitivity of expanded testing. Pre-test counseling is especially important when considering new and expanded genetic testing. Learn more about the pros and cons of panel testing as well as other testing options in the free course Genetic Testing Technology.
A "variant" is simply a change from the reference sequence and does not necessarily indicate pathogenicity. A variant may be classified as uncertain (VUS) when it has not been seen in a previous patient, or when the effect on gene function is unknown. A VUS should not be used for clinical diagnosis, risk prediction or changes in management until more is understood about the variant. Until the VUS can be reclassified as pathogenic or benign, patient management decisions should be based on family history and personal risk factors. Learn more about VUSs and other possible outcomes of genetic testing in the free course, Interpreting Genetic Testing Results.
The clinical significance of any genetic testing result depends strongly on the patient's personal and family histories, as well as the technical limitations of the specific test ordered. A negative test result is reassuring, but does not completely rule out hereditary cancer susceptibility. Additionally, in unaffected individuals, a negative test result is not fully informative without knowing if a causative variant has been identified in an affected family member (see #2 above and the Interpreting Results course for more information).
For more education and practice with risk assessment and genetic testing, see JAX’s full portfolio of free online CME modules.