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If you’ve heard concerns about false positives in cancer testing, it’s important to understand that not all cancer-related tests are looking for the same thing.
Some tests are designed to look for signs that cancer may already be present. Hereditary cancer risk testing does something different: it looks for inherited genetic changes associated with an increased risk of developing certain cancers.
That distinction changes what a “positive” result means and how concerns about false positives should be understood.
Multi-cancer detection (MCD) tests, sometimes called multi-cancer early detection (MCED) tests, are designed to look for biological signals that may indicate cancer is present in the body. Depending on the test, a single blood sample may be used to screen for signals associated with several different types of cancer.1
These tests are used in people who may have no symptoms or known cancer diagnosis. A positive result does not diagnose cancer. Additional imaging, procedures, biopsies or other diagnostic testing may be needed to determine whether cancer is actually present.1,2
Like other screening tests, MCD tests can produce false-positive results. A false-positive result is a positive test followed by further evaluation that does not find cancer. The National Cancer Institute identifies false-positive results, additional diagnostic procedures, uncertainty and anxiety among the potential harms of MCD testing.2
What is the test detecting when that happens? MCD tests look for biological signals that may be associated with cancer, such as changes in DNA or RNA, patterns of DNA methylation or fragmentation, proteins, or other substances found in the blood. A positive result means the test detected a signal that met the test’s criteria for a possible cancer signal. It does not necessarily mean that the signal came from a cancer that is present.2
There is also a basic challenge inherent in screening people who do not have a known cancer diagnosis. When a disease is relatively uncommon in the population being screened, even a test with high specificity can produce some positive results in people who do not have the disease. In screening, the likelihood that a positive result actually represents cancer depends not only on how well the test performs, but also on how common the disease is in the population being tested.3
Kadance’s Hereditary Cancer Risk Test answers a fundamentally different question.
It does not look for cancer or for biological signals suggesting that cancer may be present. Instead, it analyzes the DNA a person was born with for inherited genetic variants associated with an increased risk of certain cancers.
A positive hereditary cancer risk result means that a pathogenic or likely pathogenic genetic variant associated with increased cancer risk was identified.
It does not mean cancer has been detected. And it does not mean that the person will definitely develop cancer.
Inherited cancer-associated variants affect risk, not certainty. The amount of risk can differ based on the gene, the particular variant and the cancer involved, as well as factors such as age, personal medical history and family history.
The value of identifying an inherited risk factor is that the information can help an individual and their healthcare provider have a more informed conversation about whether different cancer monitoring or risk-reduction strategies may be appropriate.
Genetic testing technology makes it possible to analyze a very large number of genes at once. But when it comes to hereditary cancer risk, a larger panel does not automatically mean more clinically useful information. Larger panels can increase the number of variants of uncertain significance (VUSs) that are identified.
Some hereditary cancer panels assess many more genes than Kadance’s 26-gene panel. As panels get larger, they are also more likely to identify variants whose clinical significance is not yet well understood.
A study of 1.69 million people who underwent hereditary disease genetic testing found that 41% had at least one VUS, and 31.7% had results containing only VUS findings. The number of VUSs per person increased as more genes were tested, and the rate of VUS-only results also increased as panel size grew. VUS findings do not provide a clear answer about cancer risk and can create uncertainty for patients and healthcare providers. Of the unique VUSs that were later reclassified in the study, 80.2% were ultimately classified as benign or likely benign, and it took an average of about 31 months for those variants to be reclassified.4
Kadance takes a more focused approach.
Kadance’s Hereditary Cancer Risk Test analyzes 26 genes selected based on strong scientific evidence linking them to increased cancer risk and established guidance supporting how those findings can inform healthcare decisions.
The panel includes genes associated with well-established hereditary cancer conditions, including BRCA1 and BRCA2, as well as MLH1, MSH2, MSH6 and PMS2, which are associated with Lynch syndrome.
Kadance’s panel includes genes associated with CDC Tier 1 genomic applications, as well as additional genes supported by strong scientific evidence. The CDC defines Tier 1 genomic applications based on evidence-based guidelines and recommendations. Hereditary breast and ovarian cancer and Lynch syndrome are among its Tier 1 cancer applications.5
Gene inclusion is evaluated using established evidence-based resources, including CDC genomic recommendations, ClinGen, ClinVar and NCCN Guidelines. Kadance’s Science page identifies these resources as part of its gene-selection process.6
A VUS is not the same thing as a false positive. The genetic variation may truly be present. What is uncertain is what that variation means.
That distinction matters because a VUS should not be treated like a confirmed hereditary cancer risk finding. Guidance from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology states that a VUS should not be used in clinical decision-making. NCCN guidance likewise recommends that a VUS alone should not change medical management.7,8
Kadance’s goal is not to identify every genetic difference that might someday turn out to be associated with cancer. It is to provide information supported by strong enough scientific evidence to have meaningful relevance to a person’s cancer risk and healthcare decisions.
That focused approach can also help avoid unnecessary worry around findings whose significance is not yet understood. Someone should not be left believing they have a confirmed increased cancer risk or feel compelled to pursue additional medical testing or procedures based solely on a genetic finding that science cannot yet interpret.
There is an important distinction between accurately detecting a genetic variant and determining what that variant means for cancer risk.
Kadance’s Hereditary Cancer Risk Test is performed by Kailos Genetics, Kadance’s CAP-accredited and CLIA-certified laboratory specializing in next-generation sequencing.
Laboratory validation evaluated the accuracy, sensitivity, specificity, repeatability and reproducibility of the test. Kailos established a 95% minimum requirement for each reported validation measure, and the Hereditary Cancer Risk Test exceeded that threshold across every measure. Results ranged from 97.5% to 100%, depending on the measure evaluated.6
No laboratory test should be described as incapable of producing an error. In hereditary genetic testing, a false-positive result can occur if a laboratory incorrectly identifies a genetic variant as present.
There is also a separate question of how a genetic variant is classified and what that finding means for cancer risk. A variant can be present without being pathogenic, which is one reason careful variant classification matters.
That distinction is important when comparing concerns about false positives across these very different types of tests.
A positive result from Kadance’s Hereditary Cancer Risk Test can identify an inherited genetic factor associated with increased cancer risk. That information can help inform conversations with a licensed physician or genetics professional about appropriate next steps.
A negative result does not mean that someone has no risk of cancer. Most cancers are not caused by a single inherited genetic variant, and factors such as age, environment, lifestyle, personal medical history and family history can also contribute to risk.
Kadance’s test does not analyze every gene that has ever been associated with cancer, and it does not diagnose cancer.
Its purpose is more focused: to identify inherited cancer risk where the scientific evidence is strong enough for the finding to provide meaningful information for an individual and their healthcare provider.
For more information about how hereditary cancer panels work, read What Is an Inherited Cancer Risk Panel?
You may also want to read Genetic Testing for Cancer Risk: What It Shows and Who Should Consider It, which explains what hereditary cancer risk testing can and cannot tell you.