Study Finds Universal Genetic Testing Uncovers More Inherited Mutations vs Guideline-Based Genetic Testing
Universal genetic testing may uncover inherited genetic mutations, and could individualize cancer therapies, improve survival, and strengthen the use of precision medicine. In a new study published by N. Jewel Samadder, MD, and colleagues in JAMA Oncology, researchers conducted genetic testing in more than 3,000 patients who were diagnosed with cancer. In all, the scientists found that one in eight patients with cancer had an inherited cancer-related gene mutation—and that these mutations would not have been detected in half of these patients if testing had been conducted using a standard guideline-based approach.
Dr. Samadder also presented these findings at the American Society of Human Genetics 2020 Virtual Meeting (Abstract 1427).
“We found that 13.5% of patients had an inherited mutation in a gene associated with the development of their cancer,” said Dr. Samadder, a gastroenterologist and hepatologist at the Mayo Clinic, in a press release. “Everyone has some risk of developing cancer, and in most cases, the disease develops by chance. However, some people are genetically predisposed to developing certain types of cancer, such as breast or colon cancers.”
“This prospective, multicenter cohort study found that universal multigene panel testing among patients with solid tumor cancer was associated with an increased detection of heritable variants over the predicted yield of targeted testing based on guidelines. Nearly 30% of patients with high-penetrance variants had modifications in their treatment.”— N. Jewel Samadder, MD, and colleagues
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Although many mutations that cause cancer happen by chance in a single cell, the study confirms that nearly 10% to 25% are inherited mutations that set off a cycle of events that can lead to cancer. Dr. Samadder also explained that uncovering these hidden inherited genetic mutations could lead to opportunities for cancer management in families and targeted cancer therapies.
Study Methods and Findings
In the 2-year Interrogating Cancer Etiology Using Proactive Genetic Testing (INTERCEPT) study, Mayo Clinic provided free genetic testing and counseling to 3,084 patients as part of their standard cancer care. The project—representing the largest known multicenter study of universal testing of patients with cancer—included patients with a broad mix of cancer stages and types, including breast, colorectal, lung, ovarian, pancreatic, bladder, prostate, and endometrial cancers.
Pathogenic germline variants were found in 397 patients, including 282 moderate- and high-penetrance cancer susceptibility genes. Variants of uncertain significance were found in 1,415 patients. In total, 92 patients had incremental clinically actionable findings that would not have been detected by phenotype or family history–based testing criteria.
During the study, when the researchers examined the effects of a genetic mutation discovery, they found that 28.2% of the patients with the highest-risk cancer genes had a change in their medical management, including the type of surgery or chemotherapy they received.
“This targeted treatment would have been lost if the patients had not received genetic testing,” emphasized Dr. Samadder.
Dr. Samadder said that equally important to the discovery of a patient's inherited cancer mutation is the potential for patients to share the heritable cause of their disease with their relatives, allowing family members to pursue care for earlier disease detection and cancer management.
The researchers found that the standard guidelines physicians relied on to determine which patients with cancer should undergo genetic testing were only able to identify 48% of the patients with an inherited genetic mutation.
“More than half of the patients who developed cancer due to inherited mutations were being missed—and that has major implications for family members,” said Dr. Samadder.
The study authors concluded, “This prospective, multicenter cohort study found that universal multigene panel testing among patients with solid tumor cancer was associated with an increased detection of heritable variants over the predicted yield of targeted testing based on guidelines. Nearly 30% of patients with high-penetrance variants had modifications in their treatment.”
Disclosure: Genetic sequencing, deletion and duplication analysis, and variant interpretation was performed at Invitae Corporation. Support for this project was provided by the Mayo Transform the Practice Grant, Mayo Clinic's Center for Individualized Medicine, Desert Mountain Members' CARE Foundation, the David and Twila Woods Foundation, and a Faculty Career Development Award from the Gerstner Foundation (NJS). For full disclosures of the study authors, visit jamanetwork.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.