Physician Education Needed Too

There is also a need for better physician preparation  to interpret and communicate test results to patients. There simply aren’t enough genetic counselors for the increasing number of patients undergoing these tests, noted medical oncologist Mark Robson, MD, director of the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center in New York, NY, and a member of ASCO’s Cancer Prevention Committee.


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When the clinical evidence base is ambiguous, positive results from multiplex tests might increase a patient’s risk of unnecessary prevention efforts and their anxiety over seemingly indicated interventions.2,3

For example, some CDH1 mutations increase the risk of diffuse gastric cancer and lobular breast cancer, which could lead some patients with no family history of gastric cancer to consider prophylactic gastrectomy.2,3

The temptation might be for those who are not very familiar with the empirical literature to “default to what they do know, for instance, applying recommendations appropriate for BRCA1 or BRCA2, like recommending the removal of ovaries, or a bilateral mastectomy, in cases where they should not be applied,” Dr. Robson says. “It’s hard to know how much of this happens, but it clearly is a concern.”

“There’s nothing inherently wrong with the concept of multiplicity; we’ve been doing multiple-genes testing for a long time,” said Dr. Robson. “You can even think of BRCA1/2 testing as a very small (two-gene) panel.”

The real challenge is not the concept of simultaneous multiple-gene testing, but deciding exactly what genes really belong in the panel, experts agreed.

“That’s the million-dollar question,” said National Society of Genetic Counselors (NSGC) President Joy Larsen Haidle, MS, when asked if multigene panels are ready for routine clinical use.

“Not all panels are created equal. Sometimes, a bigger panel isn’t necessarily better. It’s very important that patients meet with a genetic counselor and continue follow-up conversations as information matures.”

 “Some panels are fine and some are not, and the ones that are more challenging are those that include genes for which we have no clear management guidelines when an abnormality is found,” Dr. Robson stated. “That happens to describe most of the multiplex tests on the market.”

Other than the BRCA1/2 test results, the rate of clearly actionable results from multiplex panels is unclear and appears to be low overall—perhaps less than 1%, Dr. Robson noted. However, the likelihood of mutations among genes for which clear clinical guidelines exist, is about 4%.4

And just because a test result is actionable does not mean that it has clinical utility—that it will actually change patient outcomes, Dr. Robson was quick to add.

New Genetic-Counseling Paradigms

Experts agree that the counseling model must change as multiplex testing becomes more common.5,6 The traditional approach for targeted single-gene or a two-gene tests has been pretest and post-test counseling and discussion of the predictive value of the test and what options are available for patients who receive positive results.

“That’s a lengthy process,” said Dr. Robson. “The problem is, with a 23-gene panel, that’s just impractical. It’s even difficult for the four or five genes that may be clearly meaningful (on a panel).”

Instead, multigene panels demand a more “generic” and flexible education process for patients, like the “tiered and binned” approach6 developed by Dr. Bradbury and others, said Dr. Robson.

“I think the model’s moved toward more generic counseling up front—albeit not completely generic—and then applying a lot more specificity on the back end. We’re de-emphasizing detailed front-end, pretest counseling and essentially asking the patient to allow us to interpret on the back end, depending on their specific findings.”

The genetic counseling model “has been shifting dramatically over the past 18 months,” confirmed Larsen Haidle. “If I have 20 genes on a panel, do I need to go through all the nuances and details for every single gene, up front, which is what I used to do? Or do I just talk about the genes globally, generally, and then offer a much more detailed and targeted discussion once the results come in? The latter option is the more reasonable approach for the provider and may be more useful for the patient.”

In the still-investigational tiered-and-binned model of genetic counseling, indispensable information is given to all patients, and then specific “binned” information is offered to patients in different groups, based on clinical and family-history information, to avoid information overload.6

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Dr. Bradbury and colleagues are pursuing longitudinal studies of the model, and are studying the effects of phone versus in-person communication of gene panel results.

“For genomic medicine to move forward, it really has to be this way,” Dr. Robson adds. “Ultimately, we cannot counsel somebody for all 20,000 genes in the exome, if we move to whole-exome profiling. We need to give enough information for the patient’s decision to go forward or not, for testing as a whole.”

Information overload is a potential problem for both patients and physicians, Drs. Roberson and Bradbury warn.