One of the most common questions people ask is, “How do I interpret Foundation One test results?” We want to help you understand the test itself, as well as the report generated from its results. As always, we recommend consulting your physician when making any medical decisions.
What Does Foundation One Test?
The purpose of the Foundation One test is to identify changes in tumor cell DNA. Each cell in your body has a complete copy of your DNA and tumor cells are no different. Generally speaking, DNA is made up of functional units which are known as genes.
Your DNA is sometimes referred to as your genetic code because it instructs cellular processes. This is similar to the way that computer code instructs computer processes. When there are errors in your DNA code, cells can start malfunctioning. Just like an error in computer code can cause problems in a software program.
Tumors are composed of malfunctioning cells and unsurprisingly tumor cell DNA is full of errors. Damaged or altered versions of your DNA are often referred to as mutations. Sometimes a DNA mutation occurs in a harmless gene. Other times a mutation can causes a serious glitch that results in unrestrained cell division. Cell division is when one cell divides and becomes two cells.
Click to See What Cell Division Looks Like: Cell Division Gif
Gene Mutations And The Foundation One Test
If an error in DNA leads to a glitch in the functions of a cell, then division might occur more frequently than normal. Increased rates of cell division can lead to the growth of a tumor. Many different types of errors can occur in DNA and each error has the potential to negatively mutate the affected gene.
Depending on which gene is mutated, normal processes like cell division, metabolism or even tumor suppression can be negatively impacted. If a cell does not correct the error, the DNA will become permanently mutated. Each cell division will create a sister cell harboring that same mutation. Sometimes those mutations compound and lead to errors in other important genes. This can speed up tumor growth.
Over several decades scientists have cataloged common DNA errors and mutated genes found in tumors. The Foundation One test is designed to detect the types of errors and the specific genes that are mutated. In total this test assesses changes in over 300 genes that have been found to influence tumor growth.
Each patient will receive a detailed report with a table that looks similar to this:
This table has four sections and they are:
Column 1: Genomic Findings Detected
The first column, “Genomic Findings Detected,” displays mutated genes in your tumor’s DNA. The bold text is the name of the mutated gene and the lighter text is the specific type of mutation. There are many mutations that occur in DNA. Sometimes the type of mutation can confer treatment decisions. However, not all mutations can be targeted by existing therapies.
The first row in the above table displays a mutation in the ERBB2 gene. The mutation was a gene amplification. Amplification means that the gene was copied multiple times in tumor-cell DNA. In a gene like ERRB2 this could result in much more rapid cell division. Foundation One includes the word, “Equivocal,” when they believe a result needs secondary testing.
Other information such as, “Splice site…” , “Loss of exons…” , or a string of letters and numbers with, “*”, refer to specific changes to the coding sequence of the gene.
Tumor Mutation Burden
“Tumor Mutation Burden,” is also reported in this section. This doesn’t explain a specific gene mutation but it can be useful information. The burden is characterized as high, low or intermediate. Research suggests that a high tumor mutation burden may predict response to immunotherapy.
You might also see, “Microsatellite status,” in your report. This analyzes specific regions of DNA that are important but do not code for a gene. Sometimes errors occur in those microsatellite regions and the report will state if your microsatellite instability is, ‘high’, ‘low’, ‘stable’, or ‘unknown.’ If your report says you have high microsatellite instability, then you might have a genetic disease in mismatch repair genes (MMR). Some research suggests that immunotherapy is more effective against tumors with high microsatellite instability status.
Column 2: FDA Approved Therapies In Your Tumor Type
The second column, “FDA Approved Therapies In Your Tumor Type,” tells you therapies that are FDA approved for both your tumor type and your specific DNA mutation in that row.
In the first row, the table displays the drug, Afatinib. Afatinib is approved for use in the patient’s Lung Adenocarcinoma tumor (tumor type will be written at top right of the chart) and Afatinib targets the ERBB2 gene mutation detected by Foundation One testing. When a drug is approved to treat a mutation found in your tumor type, it is referred to as, “On-label use,” which means drug costs will likely be covered by your health insurance.
Column 3: FDA Approved Therapies In Other Tumor Types
The third column, “FDA Approved Therapies In Other Tumor Types,” tells you therapies that are FDA approved for other tumor types, but target DNA mutations found in your tumor.
In the table we see that the drugs Ado-trastuzumab emtansine, Lapatinib, Pertuzumab and Trastuzumab are all approved to target the ERBB2 gene. Those drugs are approved for use in at least one tumor type; however, they haven’t been approved for use in Lung Adenocarcinoma, the example patient’s tumor type.
Using drugs that are approved in other tumor types but not your own is referred to as, “Off-label use,” which is not usually covered by health insurance. Off-label drugs can be prescribed by your physician then legally purchased at full price. Note that off-label drugs may work in tumor types that have not yet been approved.
Column 4: Potential Clinical Trials
Rows in the last column, “Potential Clinical Trials,” will either say, “None,” or, “Yes, see clinical trials section.” The clinical trials section lists ongoing trials for investigational drugs that target mutations found in your tumor’s DNA.
Each patient’s Foundation One report will include a clinical trial section that looks similar to this:
How to interpret the clinical trials section of your Foundation One report:
If you are considering clinical trials, there are a couple important pieces of information in this table. First, consider the trial, “Phase.” Phase 1 trials involve dose escalation to determine the drug’s biologically active and safe dosage.
The first patient cohorts receive very low dosages, which means some patients in phase 1 trials will not receive a biologically active dosage. That isn’t good if you need to cure your tumor.
Phase 2 trials use a dosage that has already shown biological activity. Phase 2 trials also attempt to show some efficacy which – differentiates them from Phase 1 trials. Keep in mind that a hint of efficacy isn’t known until the end of the trial. At this stage there is continued investigation to determine the best and safest dosage.
Phase 3 trials are the most important trials because they’re randomized, blinded and controlled. Blinded means the investigators (meaning clinical staff and researchers) don’t know which patients are receiving the study drug. Controlled means some patients will not receive the study drug, they’ll receive existing standard-of-care treatments. Randomized means that the patients who receive the study drug are randomly selected to prevent ‘gaming’ the patient cohort.
The column labeled, “Targets,” also has useful information. This section tells you the specific gene(s) targeted by the drug. A drug targeting multiple mutated genes in your tumor may be a better choice than drugs that hit only one target. Oftentimes the more ways you can hit your tumor the better.
How To Use The Cure-Hub Clinical Trial Finder
You can use Cure-Hub to find any phase 2 or 3 therapeutic cancer trials. The best way to search for a specific trial is to use the NCT ID – the trial’s unique identifier. This is in the last column of Foundation One’s clinical trial table. To do this, plug the NCT ID into the keyword section on the Cure-Hub Clinical Trial Finder.
If you login to Cure-Hub, you can save the trial to your profile. This makes it easy for you to read about, compare trials and share information with your physician. In our, “How To Enroll In a Trial,” section we have detailed instructions for contacting and enrolling in a trial.
You can also use drug or gene names to search for other clinical trials that might help treat your tumor. As always we are available to answer questions regarding Foundation One testing or finding the right clinical trial for you.
Here is a link to Foundation One’s guide to interpreting their test results: Link