Molecular Profiling Terms To Know
- In breast cancer, many different kinds of tests determine the makeup of your cancer.
- The tests your doctor may do vary based on your stage of breast cancer, medical history, and family history.
- These tests can determine your subtype of breast cancer.
- They can indicate your eligibility for certain treatments and how well you would likely respond to certain treatments.
- Results also may indicate how likely your cancer is to recur.
- They may also help your doctor find you a clinical trial.
What Is Molecular Profiling And Next-Generation Sequencing (NGS)?
“Molecular profiling involves the use of various technologies to understand the underlying characteristics of the tumor found in your cancer by giving us specific information on the molecular and genetic makeup of that tumor,” Dr. Abdou explains.Read More
- Whether you would benefit from certain treatments and targeted therapies.
- If your cancer is likely to come back.
- Whether other family members may be at risk for certain kinds of cancer.
- If you qualify for potential clinical trials.
How Is Molecular Profiling Conducted?“To perform molecular profiling, usually doctors take a sample from your tumor and look for abnormal genes that may be present,” Dr. Abdou says. This is called somatic or tumor-based testing. It is considered the most accurate way to obtain information on gene defects in your tumor. Knowing these defects allows your doctor to find more targeted treatments for you.
The tumor sample is often taken from the tissue biopsy saved from when you were first diagnosed with breast cancer. But sometimes, that is not a possibility.
“Sometimes we actually get the biopsy, and there is not enough tissue, or the quality of the tissue is not adequate for molecular profiling,” Dr. Abdou explains. “In these circumstances, a blood test can actually be sent for molecular profiling, and this test can capture the DNA that is shed from the tumor in the blood. And genomic alterations can be detected through that blood test.”
What is a Liquid Biopsy?
The blood test that Dr. Abdou is referring to is also a type of NGS called liquid biopsy. It looks at DNA from dead tumor cells that have moved from your tumor into your bloodstream called circulating tumor DNA (ctDNA). The test can be quicker and easier than tumor-based testing – especially if you no longer have a tumor biopsy to test. Results also come back fast – sometimes in just days to a week, compared to tumor-based NGS test results, which can take up to a month. But liquid biopsy is less sensitive – and can sometimes miss important diagnostic results.
“While the majority of the tumors do shed DNA in the blood, in less frequent circumstances, alterations cannot be detected through a blood test. And in these circumstances, a biopsy is actually needed for further molecular testing.”
Many doctors also recommend doing tumor-based NGS and liquid biopsy together to get the best of both worlds – quick answers from a liquid biopsy that then can be reinforced by the more reliable results from tumor-based NGS testing.
Testing After New Breast Cancer Diagnoses
Pathologic testing has been at the heart of breast cancer treatment for many years. It measures percentages of certain protein markers in your tumor. Those levels can give your doctor a sense of what kind of cancer you have, which can then dictate the next best steps in your treatment. Breast medical oncologists like Dr. Abdou consider this testing a must-do right after diagnosis:
“When a diagnosis is just made, the first step is to look at the tumor markers such as receptors for estrogen, progesterone, and HER2. These are usually determined at the time of the initial biopsy,” Dr. Abdou says. “This is important for treatment management moving forward, and it also helps us determine what additional tests we need for that particular subtype of breast cancer.”
Another test that is important to do after diagnosis is genetic or germline testing. Unlike NGS testing, which looks at genomic changes specifically in your tumor, germline testing looks at the DNA you were born with and inherited from your parents.
“This is a blood test that determines whether you have inherited genes that could increase your risk of developing another breast cancer down the line or other types of breast cancer and such genes. Examples of such genes include BRCA1 and BRCA2 mutations,” Dr. Abdou says.
Results of all these different tests help provide you and your doctor a clearer picture of how likely your cancer will come back, whether you are likely to develop a different kind of cancer, or if there are treatments available to you based on your cancer makeup.
What Kind of Testing is Recommended For Metastatic Breast Cancer?
It is important to ask your doctor about NGS testing in early-stage breast cancer, but it is not yet considered a standard of care. In contrast, it is considered very important to do in advanced or metastatic breast cancer. NGS test results in metastatic breast cancer look for additional DNA mutations that may have an effective targeted therapy.
On top of that, Dr. Abdou says it is very important to do a repeat biopsy of your tumor and re-test tumor markers. Here’s how she typically proceeds:
“We usually recommend a repeat biopsy of the tumor from a spot where the cancer has spread. And that’s, of course, if it’s safe to biopsy that spot,” Dr. Abdou says. “Examples of such spots would be lung, liver, and bone. Those are examples of where we would obtain a biopsy in metastatic disease. The biopsy is really to confirm that the cancer is indeed metastatic breast cancer.”
Re-testing the tumor markers is also very important. Dr. Abdou continues:
“We also like to repeat the tumor markers, which are the receptors, including estrogen, progesterone, and HER2, because while in most circumstances the tumor markers remain the same as the primary tumor that started in the breast, in some circumstances, these markers change.”
Doing another biopsy and re-testing the tumor markers gives your doctor a better sense of how your cancer has evolved. On top of that, Dr. Abdou also considers, in certain circumstances, doing immunohistochemistry (IHC) to test for PD-L1 protein levels:
“This marker is specifically checked in patients who have metastatic triple-negative breast cancer to determine what type of therapy you’ll be eligible for,” Dr. Abou says. “The PD-L1 marker will help us determine whether your tumor will respond to immunotherapy.”
If high amounts of PD-L1 are detected in your cancer cells, an immunotherapy called an “immune checkpoint inhibitor” could be a good option for you – especially if you have triple-negative metastatic breast cancer. That means your cancer does not have the estrogen receptor, progesterone receptor, or HER2.
Why Does Molecular Profiling Matter?
As cancer treatment evolves, healthcare providers look for new, effective, and minimally invasive ways to treat you. Results from these tests for breast cancer, whether it’s next-generation sequencing (NGS), germline, PD-L1, or pathology testing, can help guide medical oncologists like Dr. Abou in the right direction:
“These tests allow us to personalize our care and personalize our treatment to where we not only prolong patients’ lives, but we also minimize suffering from the disease and toxicity from the treatments.”
Types of NGS Testing On The Market
There are a number of tests you may encounter, depending on where you are getting treatment and what you are getting treatment for. Here are some of the common ones currently on the market:
- FoundationOne®CDx looks at 324 genes in solid tumors and says it can takes up to 12 days for results. Test results include microsatellite instability (MSI) and tumor mutational burden (TMB) to help inform immunotherapy decisions.
- OmniSeq Insight provides comprehensive genomic and immune profiling for all solid tumors. It looks for 523 different genes. Test results include microsatellite instability (MSI) and tumor mutational burden (TMB), as well as PD-L1 by immunohistochemistry (IHC).
- Cobas EGFR Mutation Test v2 identifies 42 mutations in exons 18, 19, 20 and 21 of the epidermal growth factor receptor (EGFR) gene. It is designed to test both tissue and plasma specimens with a single kit, and allows labs to run tissue and plasma on the same plate simultaneously.
You should ask your healthcare team if the brand of molecular testing they are doing is optimal for your cancer type.
Questions To Ask Your Doctor
- What molecular testing is right for my breast cancer?
- Has germline or genetic testing been done?
- Have we tested levels of estrogen receptor, progesterone receptor, and HER2?
- Should a new biopsy be performed?
- How do the results of these tests impact my treatment?
- How much will testing cost me?