LA JOLLA, California — Screening patients for genes that predispose them to cancer provides clinical and economic benefits, according to a genetic researcher.
"You can have large-scale, high-throughput, routine testing. We're doing about 200 a week currently, and it's fast and affordable," said Nazneen Rahman, PhD, from the Institute of Cancer Research and Royal Marsden Hospital in London, United Kingdom.
Her center uses a cancer panel (TruSight, Illumina) that requires only 50 ng of DNA, has a low failure rate, can be processed quickly at a volume of up to 576 samples per week, and costs only £300 (US$452) per patient, she reported here at the Future of Genomic Medicine VIII.
"Cancer predisposition" refers to genes in which germline mutations have been shown to confer moderate to high clinically important risks for cancer. Probably the best known of these genes are BRCA1 and BRCA2, which significantly increase the risk for breast and ovarian cancers.
Knowing a patient has a cancer predisposition gene can improve diagnosis, allows clinicians to optimize treatment and follow-up, and, in some cases, can help identify appropriate targeted therapies.
In addition, "cancer predisposition genes offer us opportunities to implement risk reduction and cancer prevention in relatives," Dr Rahman said.
She described the Mainstreaming Cancer Genetics program she directs, which is designed to make screening for cancer predisposition genes part of routine oncology visits. The program involves integrating genetic sequencing, analysis, and interpretation into a clinical report that physicians and patients can act on.
The panel her team developed, in collaboration with Illumina, is commercially available to anyone who wants to use it, Dr Rahman said.
The panel tests for 97 cancer predisposition genes and gene regions, 260 genome-wide association scan single-nucleotide polymorphisms (SNPs), and 24 fingerprinting SNPs. Together, these elements comprise 0.01% of the genome.
"For clinical genetic tests, your analysis pipeline has to be fast, it has to be totally reliable, and you need a pretty short hands-on time. If you need a bioinformatician to do each your tests, that's really going to ramp up your costs," Dr Rahman explained.
But just having a relatively low-cost genetic panel will not change clinical practice. That will require "integration of multiple disciplines and an appetite for change," she said.
The actual testing time spent with each batch is less than 1 minute, and the analysis, which takes 6 to 8 hours for 96 samples, can be done automatically overnight.
The panel test yields hundreds of genetic variants, but the clinical importance of most variants is not known. To avoid overmanagement, it is essential that each variant is classified as pathogenic, likely pathogenic, of uncertain significance, unlikely to be pathogenic, or nonpathogenic.
"If you have found something that is rare, all you have shown is that it is rare. You have to have something else before you can say that it's pathogenic," Dr Rahman explained.
More than 95% of the process of identifying and analyzing variants can be automated, but a small percentage of variants still require "expert hand curation" by people "who really know those genes, really know those diseases, and really know those variants," she explained.
At her center, the goal is to move genetic testing from the sidelines to the center of medicine. They started by looking for BRCA mutations in patients with ovarian cancer. More than 15% of ovarian cancers are caused by germline mutations in BRCA, she said.
A trained cancer team member provides each patient with an information sheet, discusses testing for BRCA, obtains consent, draws blood, and forwards it to the lab. Patients who opt for a more detailed discussion before providing consent are referred for a genetics consultation.
The results are sent to the patients and the cancer team. If a mutation is identified, the patient is sent for further follow-up to discuss the clinical significance and management options.
To date, Dr Rahman and her colleagues have offered the test to 207 women with ovarian cancer. The 33 patients (16%) who tested positive for a BRCA mutation were offered chemotherapy with a poly (ADP-ribose) polymerase (PARP) inhibitor and management for enhanced breast cancer risk.
In addition, more than 80 of their relatives have been informed of their risk profiles, and 39 have been tested for mutations.
"Every single patient we offered this test to wanted it," Dr Rahman reported. All patients said they were satisfied to have been tested during an oncology appointment, and 98% said they understood that the results could have implications for themselves and their families.
The availability of testing in the cancer clinic and the consenting process received unanimous approval from clinicians.
The system they established is both efficient and cost-effective, Dr Rahman said. There has been a four-fold increase in throughput, testing with the panel is one-quarter the cost of testing with traditional sequencing, and results are returned much faster with the panel than with older methods of testing (4 vs 21 weeks).
Because of the cost savings, the team has been able to expand the testing of women with ovarian cancer in their treatment area yet stay within the budget established by the National Health Service, she pointed out.
The model Dr Rahman and her colleagues have created is "exquisitely cost-effective," and would likely have broad and positive implications for the integration of genetic testing into medical practices on this side of the Atlantic, said Brian Leyland-Jones, MB BS, from the Avera Medical Group in Sioux Falls, South Dakota.
But he noted that oncology practices in the United States are often under pressure to use more established genetic panels marketed by Myriad Genetics, Ambry Genetics, and other companies.
Dr Rahman said that no matter who develops the gene panel, the key to making the approach work efficiently is a high-volume, high-throughput, lower-overhead model, such as the one developed by her team.
The Mainstreaming Cancer Genetics program is supported by Wellcome Trust. Dr Rahman and Dr Leyland-Jones have disclosed no relevant financial relationships.
Future of Genomic Medicine (FoGM) VIII. Presented March 6, 2015.
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Cite this: Clinic Rolls Out Affordable Cancer Predisposition Screening - Medscape - Mar 10, 2015.