Clinicians are ordering more comprehensive gene tests
to look for mutations carrying higher risks of hereditary cancer
These multigene panels are raising questions about the scope of information being collected as the science and the industry move toward increasingly advanced sequencing.
Researchers are learning more about the different genes and variants that put a patient at risk for developing hereditary cancers such as colon cancer and breast cancer. As a result, a growing number of clinical laboratories now test for a wider range of high-risk, medium-risk, low risk and even emerging-risk genes.
Another factor is last year's Supreme Court ruling that companies cannot patent human DNA. Until the June 2013 decision, Myriad Genetics was the only company in the U.S. that offered testing for the BRCA1 and BRCA2 genes. Women with mutations of those genes have a higher risk of hereditary breast and ovarian cancers.
Since the ruling, competing labs have started to offer BRCA testing, including selling BRCA testing within multigene panels that also evaluate other genes understood to cause hereditary cancers. Myriad is now moving to distinguish itself in the market as one of the few makers of the newer generation of gene tests.
Myriad, which makes about 75% of its revenue from its BRACAnalysis tests, introduced a multigene panel test in September that tests for 25 genes associated with eight hereditary cancers, including the BRCA1 and BRCA2 mutations. Executives at the Salt Lake City-based company say the new MyRisk test is expected to replace BRACAnalysis by mid-2015.
Clinicians report that in the past year they have seen a rise in the number of laboratories offering multigene genetic testing for hereditary cancers. “It's still relatively early days,” said Dr. Colin Pritchard, associate director of the genetics and solid tumors laboratory at the University of Washington in Seattle. “But that's where the field is going.”
While cost is not a primary concern—most panel tests are comparable in price to testing for individual genetic tests—some genetics professionals question the inclusion of emerging-risk genes or variants of undetermined significance on panels, and whether collecting that information is clinically beneficial or possibly harmful to patients.
A study published in March in Genetics in Medicine said that multigene panels "play an important role in the diagnosis of hereditary cancer predisposition." However, the authors also noted a need for careful interpretation of results, particularly for mutations in moderate-risk genes and for patients with negative results.
There are at least four labs offering multigene panels that test for hereditary breast and ovarian cancer, including the BRCA1 and BRCA2 genes. Myriad is one. Others are Ambry Genetics, GeneDx and the University of Washington. Each company's panel is different, presenting challenges to the clinicians who must decide what panel to order.
“Not all panels are created the same,” said Joy Larsen-Haidle, a genetic counselor at the Humphrey Cancer Center in Robbinsdale, Minn.
The companies say that panel tests are more cost-effective and save time for both the providers and the patients. For example, testing for each of the four genes associated with Lynch Syndrome is more expensive than one panel test that includes all four of those genes. One round of testing also cuts down on return visits to physicians and genetic counselors.
But there may be higher costs associated with interpreting the larger volume of data, says Heidi Rehm, chief laboratory director at Partners Healthcare's Laboratory for Molecular Medicine. And individual tests remain valuable in some cases, such as when family members come in for testing.
The University of Washington has offered its BROCA panel since 2012. When the Supreme Court struck down Myriad's patent, the lab added the BRCA1 and BRCA2 genes to the now 50-gene panel, which looks for genes that predispose a patient for hereditary breast and ovarian cancers. The panel costs less than the $3,300 Myriad charges for BRCA testing, according to Pritchard.
“It's far more cost-effective and getting far better data,” Pritchard said, comparing the panel to individual BRCA tests.
But some genetics professionals question how to use all of the data that large panels gather. With some genes, the tests indicate clear risk prevention steps—the BRCA mutations, for example, might lead to a preventive mastectomy or ongoing surveillance. But some genes included in the panels are not clinically actionable, meaning that the medical community has not established care guidelines for them.
“It's certainly a valid concern in lab testing or other medical diagnostics when you test for more, you're going to have a higher pickup rate or higher sensitivity,” Pritchard said.
Myriad plans to present a study next week at the American Society of Clinical Oncology's annual meeting finding that multigene panels provide additional clinical information but also yield findings with no clear medical management choices. Of the 87 patients at Fox Chase Cancer Center in Philadelphia who underwent the MyRisk test, three patients had unanticipated test results that led to changes in clinical management. Follow Jaimy Lee on Twitter: @MHjlee