Communicating Genetic Test Results to Patients and Their Families

Communicating Genetic Test Results to Patients and Their Families


Wendy Kohlmann, MS

Marjan Champine, MS, CGC

Sarah Colonna, MD

Genetic test results have the potential to guide treatment, alert providers to increased disease risks that could require additional screening and risk reduction, and clarify disease risks for family members. However, a genetic test report does not result in these outcomes on its own. The implications of a genetic test result must be correctly interpreted and clearly communicated to patients in order for them and their family members to benefit from this technology.

The introduction of genetic testing that evaluates multiple genes simultaneously (multigene panels) is changing the landscape of genetic counseling. A re-evaluation of current approaches for presenting genetic information is now required. Multigene panels increase the likelihood of identifying genetic factors that predispose individuals to well-quantified cancer risks, but they can also create situations when patients need counseling about mutations associated with unexpected cancer risks, mutations for which cancer-management recommendations are unclear, and variants of uncertain significance (VUS).1

The fact that these multigene panels raise new challenges does not mean that these tests should not be used, and many centers across the country are already incorporating these tests into standard practice. The utilization of this new technology should, however, be accompanied by careful thought about how these complex test results will be communicated to patients in order to maximize their benefit.

Communicating Genetic Information

Effectively communicating results to a patient should begin before the test is even conducted. This is the best opportunity to determine the patient’s level of understanding and their concerns and to appropriately set their expectations about what the test results may or may not signify. Pretest counseling should focus on addressing the key components of informed consent as outlined by ASCO and other organizations.2-4

Based on the patient’s personal and family history, there are likely particular genes to be most concerned about (e.g., for a patient with early-onset breast cancer, you may be most concerned about BRCA1/2), and the patient should be educated about the genes most related to their presentation and, therefore, most likely to immediately influence their treatment.

However, providing patients with a detailed description of all genes and the risk conferred is not feasible given the numerous genes that may be included on a multigene panel. Thus, instead of a gene-by-gene approach, consider broadly defining genes into high-risk and moderate-risk categories. Discuss with patients that our knowledge about genetics is increasing, and in order to ensure that the cause of cancer in their family is not missed, the test may include other genes associated with a highly or moderately increased risk for other types of cancer. Table 1 suggests other strategies to modify key components of informed consent for multigene panel testing. Alerting patients to the range of genes included on the panel does not need to require significant time, and, in fact, may be time-neutral. To date, our center has not noted a significant increase of time spent on pretest counseling since the utilization of multigene panels. If enough time is not available to communicate the most essential points, or if the patient is already overwhelmed with other treatment-related decisions, step back and consider whether there is an urgent need to initiate the test at that moment. If not, wait until the patient has the time and mental resources to absorb this important information and its potential implications.

Key Points
Multigene panels increase the likelihood of identifying genetic factors that predispose individuals to well-quantified cancer risks, but they can also create situations when patients need counseling about mutations associated with unexpected cancer risks, mutations for which cancer-management recommendations are unclear, and variants of uncertain significance.

Pretest counseling should focus on addressing the key components of informed consent as outlined by ASCO and other organizations.

Introducing the idea that genetic testing may not result in a completely clear or expected answer before the test results are ordered allows patients to adjust their perception of genetic testing and their expectations about the type of information they may or may not glean from the test.

Providing patients with simple summaries that they can share with their families may be helpful. Providing local genetic counseling resources can offer a point of contact for the family to help coordinate referrals and ensure that the testing process moves ahead smoothly.

Discussing Unlikely Scenarios

Multigene testing increases the mutation detection rate; however, most patients still have a negative test result.5-7 Why spend time talking to patients about possible results and findings that are unlikely to happen? The portrayal of genetic testing to the general population typically focuses on high-penetrance genes, and the message is often greatly oversimplified. The complex, multifactorial nature of cancer risk does not make for good sound bites. Concepts such as moderate-risk genes, VUS, or a family still being at high risk despite a negative test result are going to be novel for most patients.

Introducing the idea that genetic testing may not result in a completely clear or expected answer before the test results are ordered allows patients to adjust their perception of genetic testing and their expectations about the type of information they may or may not glean from the test. Also, learning about the various possible test results in advance makes results less unexpected when they appear on paper.

If a patient is not familiar with the idea that genetic variation is common among people, a VUS could be very concerning. The idea that there is something different about their genetics can be hard to shake when patients were not expecting this possibility. However, addressing the possibility of a VUS during pretest counseling can help patients anticipate that a VUS is a possibility from genetic testing, rather than perceiving this to be something particularly unusual about them personally. Similarly, it may be easier to understand the magnitude of risk conveyed by a mutation in a moderate-risk gene when patients are familiar with the idea that not all genes are associated with an inevitable cancer diagnosis.

There is no way to know what a genetic test is going to identify in advance. Time spent introducing possible outcomes provides patients a chance to consider these possibilities and understand the potential implications of various test results without being tied to the immediate emotions of learning their personal results.

Communicating Results to Family Members

Regardless of whether genetic tests identify a deleterious mutation or not, there may be important implications for family members. Genetic testing is most cost-effective for our health care system when genetic test results are accurately communicated to patients and their family members.

When a patient has a negative test result, relatives may still be at increased risk for specific cancers observed in the family and, therefore, may benefit from increased screening. Genetic testing of unaffected individuals based on family history is becoming more common, but much of this low-yield and costly testing could be avoided if the family members and their clinicians are informed of any affected relative’s test results. When no mutation is identified in a family member with cancer, cancer risk estimates and screening recommendations need to be made based on the family history. Providing patients a copy of their test results to share with relatives should improve communication between family members and their doctors about testing that has already been done.

Identifying a mutation in a high- or moderate-penetrance gene often means that at-risk relatives should then be offered testing for that specific mutation. The obligation to notify relatives about genetic test results can also be daunting for a patient dealing with a personal cancer diagnosis. Although a clinician’s primary responsibility is to their patient, by ordering genetic tests, the clinician then becomes the patient’s primary resource for helping them appropriately share information with their family. Providing patients with simple summaries that they can share with their families may be helpful and has become a common practice in many cancer genetics specialty clinics. However, what is often most needed is information about where the patient’s relatives can go for genetic counseling and further testing. Family members’ motivation to act can easily be thwarted by difficulties locating a provider capable of ordering genetic tests or being given wrong information about insurance coverage or cost for site-specific testing versus full gene analysis. Providing local genetic counseling resources can offer a point of contact for the family to help coordinate referrals and ensure that the testing process moves ahead smoothly. Table 2 includes a list of genetic counseling resources. 

Table 1. Pretest Counseling Strategies for Multigene Panel Tests

 

Key Points

Rationale

Family history

ASCO guidelines recommendations for minimal family history4

  • Any cancers among first- and second-degree relatives
  • Document maternal or paternal lineage
  • Ethnicity
  • For each cancer note: age, primary site
  • Results of genetic testing in other relatives

Although a multigene panel might help “cover your bases,” understanding the family history will help anticipate the possible results from the testing and provide more appropriate follow-up care.

Why is this test being offered?

  • To guide the patient’s treatment
  • To determine the patient’s future cancer risks and screening needs
  • To determine the risks for family members

There may be several reasons for ordering genetic tests, and it is important to clarify the intent of testing. When ordered in patients with newly diagnosed cancer, patients can confuse the genetic testing information with other treatment related diagnostics.

What genes are being tested?

  • High-risk gene(s) known to be associated with the pattern of cancer in the patient/family
  • High-risk gene(s) that may be associated with other cancer risks (not necessarily related to the specific cancers in their family)
  • Moderate-risk gene(s) that are associated with small increases in cancer risk

Provide a more detailed discussion on the gene(s) most likely to influence management. Patients should be alerted to the general categories of genes included in the panel. There is concern about finding a mutation in an unexpected high-risk gene (e.g., finding Li-Fraumeni syndrome in a patient with breast cancer), and the patient being unprepared to receive these results. This is a rare occurrence, and an in-depth discussion of the pros and cons associated with the inclusion of TP53 on a panel with every patient would be difficult. Careful review of the family history should flag people who need pretest counseling that includes discussion of additional syndromes. Notifying patients in advance that a panel includes genes associated with high risks for other types also gives them the option to choose a more directed test if they feel strongly that they do not want to learn about specific cancer risks.

Possible outcomes of the testing

  • Mutation in the high-risk gene of interest
  • Mutation in a high-risk gene associated with other cancers
  • Mutation in a moderate-risk gene
  • Variant of uncertain significance (VUS)
  • No mutation identified

Genetic testing may identify mutations that clearly disrupt the gene’s function and confer cancer risk, but also may identify a genetic change without adequate data to determine the clinical significance, resulting in a VUS. Let patients know that a VUS may be noted on their report, but this information will not change management.  Finally, during the pretest counseling process, patients should be informed that a negative result (even when testing multiple genes) cannot rule out all inherited or familial risk factors.

Management

  • Implications for patients’ current care
  • Implications for future cancer screening/risk reduction

Clarifying for the patient whether you intend to immediately use the information obtained from the test result or if this test is for future planning is important for them to understand the implications.

Implications for family members

  • If a mutation is identified, should other family members be tested? If so, which family members might be at-risk?
  • If no mutation is identified, could family members still be at-risk and benefit from additional screening or management?

Patients should be informed that test result could have implications for family members. Positive, negative, and uncertain test results may need to be communicated to family members.

Table 2. Genetic Counseling Resources
National Society of Genetic Counselors nsgc.org
National Cancer Institute Cancer Genetics
Services Directory
cancer.gov/cancertopics/genetics/directory
GeneTests Clinical Directory genetests.org/clinics

Data regarding multigene tests are forthcoming as these tests become more common and as there is long-term follow up. Clearer understanding about how patients perceive multigene test results, how prepared they feel to discuss the results with family members, and the counseling strategies that can be used to maximize the benefits of multigene testing will be very valuable. Collaboration among genetic counselors, oncologists, surgeons, and nurses will continue to be necessary to ensure the information provided by genetic testing is translated accurately into clinical care that benefits patients and their families.

About the Authors: Ms. Kohlmann and Ms. Champine are genetic counselors with the University of Utah Huntsman Cancer Institute. Dr. Colonna, an ASCO member since 2012, is an instructor with the University of Utah Huntsman Cancer institute.