By: David Shifrin, PhD
Science Writer, Filament Life Science Communications

Last September, The National Comprehensive Cancer Network published an update to their guidelines for Genetic/Familial High-Risk Assessment for Breast and Ovarian cancers. This extensive document included a large section discussing the use of multi-gene panel testing. Again highlighting the uncertainty and concern, the first paragraph of the panel testing overview included the statement that “Multi-gene testing includes ‘intermediate’ penetrant genes of unclear actionability, and may reveal missense variants of unknown significance. It is for these and other reasons that they are ideally offered in the context of professional genetic expertise for pre- and post- test counseling.” Then, in the next point, “The decision to use multi-gene testing for patient care should be no different than the rationale for testing a single gene known to be associated with the development of a specific type of cancer. Testing is focused on identifying a mutation known to be clinically actionable […]”

The guidelines also review pros and cons of using panel tests. On the plus side, more and better testing means more mutations found, more potentially actionable information that can be provided to patients and their families, better surveillance and improved therapeutic intervention. On the other side of things, variability in costs and genes screened, the likelihood of finding variants of unknown significance, false negatives, and increased complexity in making medical decisions are all listed as drawbacks.

In the end, the NCCN guidelines are relatively straightforward, bordering on the obvious: “Because of their complexity hereditary cancer multigene tests should be ordered in consultation with a cancer genetics professional.” And, “[…] an affected family member should be tested first, whenever possible. The recommendations also point out that running a panel may often be more resource efficient than going through individual gene tests one by one.” Again, nothing terribly groundbreaking.

In the UK, the UK Genetic Testing Network recently posted their recommendations for new tests to be added to the National Health Service catalogue. (New Test Recommendations for 2015/16 Commissioning Year.) Although the recommendations cover genetic testing in general, the document emphasizes the use of panels to reduce cost and time to results. Panels under consideration include those for chromosome breakage syndrome, hearing loss, inflammatory bowel disease, metabolic disorders, cardiac problems and cancer, among others. A heavy emphasis was once again placed on cost savings, something particularly acute in this case based on the financial structure of the NHS.

While organizations and government agencies are looking at the issue of panel tests and working to respond to technological advances with appropriate industry guidelines, genetic counselors are dealing with things on an individual level. Indeed, the growth in panel testing has markedly altered genetic counseling practice. This is particularly true with regards to hereditary cancer, and especially breast and ovarian cancer, screening. Survey data collected by Gillian W. Hooker, PhD, CGC and Concert Genetics’ Director of Clinical Development, suggests that the “introduction of expanded gene panels” was the major driver in changes for genetic counselors’ clinical practice over the past year or two. The overwhelming majority of genetic counselors also responded that they are ordering different types of tests for “hereditary breast and/or ovarian cancer risk assessment” than they were just a year ago. (A manuscript with details of this data is in preparation.)

Cost vs benefit will always be a primary point of tension in medical care, or business in general. In the case of panel testing, the issue is exacerbated by the complexity of the technology combined with the emotional component brought into play when dealing with patients and their families.

The majority of these three posts dealt with breast and ovarian cancer screening. However, panels are available for many other diseases and disease categories. Cardiovascular disease, metabolic disorders, cystic fibrosis, inflammation and inflammatory bowel disease are just a few of the options. More are certainly on the way, and the debate about the cost, ethics, and therapeutic value of genetic panel testing will continue for the foreseeable future.

Tue. June 2, 2015