Laboratory Initiation of Cascade Genetic Testing Spurs Uptake

A laboratory-initiated, online effort to reach cancer patients’ relatives coupled with discounted genetic tests can increase rates of cascade testing, according to a study published in the January issue of the Journal of the National Cancer Institute. Almost half of patients’ first-degree relatives followed through with genetic testing when contacted by a laboratory.

“The results have been very striking, as traditional approaches to cascade testing result in only about 30 percent of relatives undergoing testing,” said coauthor Allison Kurian, M.D., from Stanford University (California), in a statement.

While cascade testing is recommended for Lynch Syndrome and Hereditary Breast and Ovarian Cancer Syndrome, in practice, there are barriers to its implementation, including cost (with tests costing more than $500), insurance restrictions (e.g., Medicare does not cover preventive genetic testing of cancer-free relatives), and confidentiality laws prevent doctors or genetic counselors from directly contacting a patient’s relatives.

This study evaluated an online initiative in which carriers of one of 30 cancer-associated genes, or their first-degree relatives, could offer low-cost testing to other at-risk, first-degree relatives. The known carrier or their first-degree relative, could apply to the family testing program by creating an online account and uploading their previous test results. In addition to those applicants with a qualifying pathogenic result, the laboratory distributed information about the program through online advertisements, at clinics, and at events for families with hereditary cancer. After initial application, the testing laboratory sent emails to first-degree relatives, identified by the applicant, inviting them to undergo multiplex sequencing of these 30 genes at an out-of-pocket cost of $50 through a CLIA-certified laboratory. The protocol required first-degree relatives with positive results to speak by phone with a genetic counselor to obtain test results and receive counseling about cancer risk.

The researchers found that over the program’s first year (September 2016 through September 2017), there were 1,101 applicants (741 carriers and 360 first-degree relatives), who invited 2,280 first-degree relatives to undergo genetic testing. Most applicants were female (78.1 percent). Just under half of invited relatives (47.5 percent) underwent genetic testing over a median of 216 days of follow-up. Of first-degree relatives who tested positive, 12.0 percent continued the cascade by inviting additional relatives to test.

“While the cascade rate might be expected to decrease with each successive invitation of relatives, the observed drop-off to 12.0 percent is likely suboptimal,” the authors write. “This drop-off could reflect limited understanding of test results, which is the major potential weakness of an online approach without in-person counseling.”

Invited female relatives were significantly more likely to follow through with testing than males (52.6 percent versus 42.0 percent). However, follow through was similar whether the carrier who invited them had a variant associated with a well-characterized syndrome or in a less well-characterized gene.

As might be expected, the authors say, 48.1 percent of tested relatives carried the identified familial pathogenic variant. However, 4.9 percent of tested relatives had a pathogenic variant in a different gene from the known familial one and 16.8 percent had a variant of uncertain significance.

“These pathogenic mutations were totally unexpected and suggest that this may reflect the prevalence in the general population of known cancer-associated mutations,” said Kurian in a statement. “It addresses a long-standing question in the field about what we might find if we routinely tested everyone.”

The genetic testing firm Color Genomics (San Francisco) partially funded the study.

Takeaway: Laboratory initiation of cascade testing may be an effective, low-cost way to overcome some of the barriers traditionally associated with adoption.