FDA Clears Genetic Test for Cancer Risk Assessment

The U.S. Food and Drug Administration has officially granted de novo marketing approval for the Invitae Common Hereditary Cancers Panel. This is an in vitro diagnostic test designed to identify a wide range of genetic variations associated with an increased risk of specific cancers. It can also pinpoint potentially cancer-related hereditary variants in individuals already diagnosed with cancer. This pioneering test, the first of its kind to receive FDA marketing authorization, analyzes DNA extracted from a blood sample to detect variants in 47 genes known to be linked with a heightened risk of certain types of cancer.

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Simultaneous Testing of Multiple Genes is now a Possibility

Dr. Jeff Shuren, the director of the FDA's Center for Devices and Radiological Health, noted that this test is capable of assessing multiple genes simultaneously using next-generation sequencing, offering a swift and sensitive approach to identifying genetic variants.

This advancement is significant for public health, as it equips individuals with crucial information about their health, including potential predispositions for specific cancers. This knowledge can guide physicians in providing tailored monitoring and potential treatment based on the discovered variants.

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Cancer: One of the Leading Cause of Death

The Centers for Disease Control and Prevention reports over 100 documented types of cancer, a disease characterized by uncontrolled division of abnormal cells and their ability to invade surrounding tissue. It stands as the second leading cause of death in the United States, trailing only heart disease.

The Invitae Common Hereditary Cancers Panel is a valuable tool for identifying inherited factors contributing to various cancer types. Patients are encouraged to consult with healthcare professionals, particularly genetic counselors, to discuss any personal or family history of cancer, which can aid in interpreting test results. It's important to note that this test does not cover all known genes associated with cancer predisposition.

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Process of Genetic Testing for Early Detection of Cancer

In terms of the testing process,

1. The sample is collected at the point of care, such as a doctor's office, and then sent to a laboratory for analysis
2. Clinical interpretation of the variants relies on evidence from published research, public databases, prediction programs, and Invitae's curated variants database, using criteria consistent with established standards

Notably, some of the most clinically relevant genes identified by the test include BRCA1 and BRCA2 (linked to hereditary breast and ovarian cancer syndrome), Lynch syndrome -associated genes (MLH1, MSH2, MSH6, PMS2, and EPCAM), CDH1 (mainly associated with hereditary diffuse gastric cancer and lobular breast cancer), and STK11 (associated with Peutz-Jeghers Syndrome).

The FDA conducted a thorough review of the Invitae Common Hereditary Cancers Panel under the De Novo premarket review pathway, specifically designed for new types of devices with low to moderate risk. Invitae conducted extensive testing on over 9,000 clinical samples, achieving an accuracy rate of ≥99.0% for all tested variant types.

Risk Associated with Genetic Testing

The main risks associated with the test are the potential for false positive and false negative results and the possibility of misinterpretation of the results.

False Negatives:

can provide a misleading sense of security, potentially leading to inadequate surveillance or clinical management.

False Positives:

may lead to inappropriate healthcare and lifestyle decisions, with potential undesirable clinical consequences.

Additionally, since this test does not cover all known genes associated with cancer predisposition, and genetics are not the sole factor in cancer development, there's a risk of patients misunderstanding that they still carry some risk of developing cancer even with a negative test result.

These risks are addressed through rigorous analytical and clinical validation, along with appropriate labeling of the test. In addition to the De Novo authorization, the FDA is instituting specific controls outlining requirements for labeling and performance testing.

For example, accuracy in reporting substitutions, insertions/deletions, and copy number variants must be ≥99.0% for positive agreement and ≥99.9% for negative agreement with a validated orthogonal method. When these criteria are met, the special controls, in conjunction with general controls, ensure a reasonable level of safety and effectiveness for tests of this nature (1^✔ ✔Trusted Source
Clinical and analytical validation of FoundationOne®CDx, a comprehensive genomic profiling assay for solid tumors

Go to source).

This action establishes a new regulatory classification, implying that subsequent devices with the same purpose may undergo the FDA's 510(k) premarket process. This pathway allows devices to gain marketing authorization by demonstrating substantial similarity to a predicate device, potentially saving developers time and expenses compared to other review processes.

In conclusion, this approval is a significant milestone in the field of genetic cancer risk assessment that empowers individuals with crucial insights into their predispositions, allowing for proactive health management.

“In granting approval for the Invitae Common Hereditary Cancers Panel, we usher in a new era of personalized cancer risk assessment."

Reference:

1. Clinical and analytical validation of FoundationOne®CDx, a comprehensive genomic profiling assay for solid tumors - (https://ncbi.nlm.nih.gov/pmc/articles/PMC8926248/)

Source-Medindia