August 2015, Vol 4, No 4

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Considerations in Genetic Testing


Now that new tests are changing the landscape of genetic testing, challenges are emerging in communicating results to patients, according to presenters at an education session on “Genetic Testing in 2015: Who Owns the Data, How Do You Return Results, and Other Clinical Dilemmas.”

Multigene panels can now be offered to patients, and these allow the testing of many genes for the same price as testing for 1 or 2 genes. Although this allows detection of mutations that contribute to hereditary cancers, many genes included in the panel are not actionable (ie, treatable), and their exact contribution to cancer risk remains unknown. The detection of unclassified genetic variants is common.

How to explain all this to patients? Wendy Kohlmann, MS, CGC, Huntsman Cancer Institute and the University of Utah, said that providers can help prepare patients to receive and understand results with appropriate pretest counseling. Patients need to be educated about potential findings from multigene panels and the difference between high-risk and moderate-risk genes, she said. When these discussions are part of management, patient expectations can be appropriately managed. Moreover, once patients understand that multigene panels can convey information that does not help in their management, they may opt for testing only for high-risk genes based on family history.

Unexpected results can turn up on multigene panel testing; for example, a patient may want to know whether she has BRCA1 or BRCA2 mutations based on breast or ovarian cancer history of her first-degree relatives, and the test could identify a gene such as CDH1, which is associated with high risk of developing gastric cancer.

A finding like this raises a host of difficult questions, including whether this mutation conveys the same risk in a carrier without a family history of gastric cancer as in one with such a history, and if the patient is willing to pursue her gastric cancer risk when that was not her initial concern.

“The pretest counseling prepares patients for the possible outcomes of testing. One cannot separate preparing the patient from returning the results,” she told listeners. “It is all one process, because the pretest visit helps prepare patients, and this determines the outcome of the disclosure.”

Genetic counselors are a helpful resource in addressing these needs in the setting of a busy practice, she added.

Proceed with Caution

As multigene panel testing becomes less expensive and more accessible, the question of what constitutes “TMI” (“too much information”) takes on greater importance. At the current stage of genetic testing, William D. Foulkes, MBBS, PhD, Director, Cancer Genetics Program at McGill University, Montreal, Canada, holds the opinion that “less is more.”

He believes that many physicians presented with the results of multigene panel testing face the challenge of deciding on an appropriate treatment strategy, but such information is not known for many genes included in the panels. Given the current state of knowledge, Foulkes raised the question of whether multigene panels should be used at all. He noted that physicians might get into trouble and advises that they order multigene panels only if they are prepared to proceed with caution.

Genetic Testing Without Clinical Data?

Mark E. Robson, MD, Clinical Director, Clinical Genetics Services, Memorial Sloan Kettering Cancer Center, New York City, explained how the evidence-based approach of the Evaluation of Genomic Applications in Practice and Prevention process can help assess if genetic tests and their applications can be clinically valuable.

The determination is based on meeting 3 criteria: the analytic ability of the genomic test, clinical validity, and clinical utility. These criteria address, respectively, how well the test measures what it claims to assess; diagnostic or risk prediction accuracy of the test; the evidence of clinical outcomes, and whether it provides added value to patient care.

Robson emphasized the importance of looking beyond whether a finding is actionable to determine if it is also clinically useful. With insufficient evidence of clinical utility, the determination ultimately involves one’s personal view of the risk-to-benefit ratio associated with the test.

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