Molecular diagnostics are specialized tests doctors use to look at proteins, RNA, and DNA in and on cancer cells. When you have breast cancer, they show your doctors what’s unique about your tumor so they can better understand your cancer and help choose the best treatments for you.
Molecular diagnostics for breast cancer can do many things, including:
- Show how fast your cancer is likely to move or evolve
- Help predict what type of treatment will work best for you
- Reveal genetic mutations so your doctor can choose targeted treatments
- Check for signs that your cancer may return
These tests give your doctor a “molecular fingerprint” of your cancer, helping them not only tailor your treatment (so it’s most effective) but also understand how the cancer is behaving in your body, says Jason Mouabbi, MD, assistant professor in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas.
“It tells us how aggressive the cancer is, how aggressive we should be with the treatment and also tells us if it’s something that can be curable with certain therapies or if it’s more likely to be chronic and treated over time,” says Mouabbi.
Doctors call these tests many different names depending on how and why they do them. These include:
- Tumor testing
- Tumor genetic testing
- Tumor marker testing
- Tumor subtyping
- Genomic testing
- Genomic profiling
- Genome sequencing
- Molecular testing
- Molecular profiling
- Somatic testing
- Next-generation sequencing
Broadly, doctors look at molecular testing in three layers:
Biomarker testing. These tests look for proteins on or in cancer cells (biological markers) that show what’s fueling your cancer. Every breast cancer diagnosis starts with biomarker testing.
Gene expression profiling. These tests measure patterns of genetic activity to predict how well certain treatments will work.
Genomic sequencing. These tests scan DNA for mutations that can be treated with targeted drugs. Doctors look to this layer of testing for metastatic cancers — those that have spread to other parts of the body.
“The first layer of testing is biomarker testing, and the second layer is genetic, or germline genetic testing, says Mouabbi. “The third layer — depends on whether we are treating a cancer in the early setting or metastatic setting.
Biomarker testing
The biomarkers doctors test for in breast cancer biomarker testing include:
- Estrogen receptor (ER)
- Progesterone receptor (PR)
- HER2 (human epidermal growth factor receptor 2)
Doctors need to know which of these markers you have (or if you have none of them) to create your treatment plan. When you have one of these biomarkers, you’re “positive” for it. So if your cancer is ER/PR-positive, your treatment will be different than if it’s ER/PR negative.
If you don’t have any of these three markers, your cancer is “triple-negative.” For triple-negative breast cancer that's also metastatic, doctors may test for PD-L1.
“PD-L1 only comes into play if the cancer isn't driven by estrogen receptor, progesterone receptor, or HER2,” says Mouabbi. “PD-L1 is one of the markers the cancer utilizes to evade the immune system. And nowadays, we can target it and unleash the immune system to fight against the cancer.”
Gene Expression Profiling
This testing sees if you inherited gene mutations such as BRCA1 or BRCA2, which can raise your risk of breast cancer. If you’ve been diagnosed with breast cancer, knowing your genetic mutations can help guide your treatment decisions.
BRCA-related cancers may benefit from special drugs called PARP inhibitors. PARP stands for poly (ADP-ribose) polymerase. PARP inhibitors stop cancer cells from repairing their DNA so they can’t fix themselves, causing them to die. This is a type of treatment called targeted therapy.
Unlike biomarker testing, genetic testing isn’t automatic, so you should ask your doctor about it, says Mouabbi.
“PARP inhibitors can be very effective against those mutations, and without knowing if this mutation is there or not, we wouldn't know that the patient qualified,” says Mouabbi. “That’s why it's so important to have that test.”
Specific gene expression profiling tests
If your cancer is early-stage and hormone-driven, your doctor will typically choose hormone therapy to treat it. But some people also benefit from chemotherapy. Not all hormone receptor-positive cancers respond to chemotherapy, and chemotherapy can have many side effects. Luckily, your doctor can use gene profiling expression tests to predict whether chemotherapy would have an added effect on your cancer. They do this by helping predict the chances of your cancer coming back, or recurring.
“In the early 2000s, everybody was getting chemo, but now, we only give chemo to those who really need it, and we spare chemotherapy for those who don't need it,” says Mouabbi. “These tests really make us better physicians and create better-tailored treatment.”
Some specific gene tests include:
Oncotype DX (21-gene assay). This test is for stage I, III, or IIIa hormone receptor-positive cancers that haven’t spread to more than three lymph nodes and that are HER2-negative. It tests 21 genes and gives you a recurrence score between 0 and 100. A lower score means you have less chance of recurrence.
MammaPrint (70-gene assay). For breast cancer that’s spread to more than three lymph nodes, MammaPrint can help predict how likely your cancer is to return in a distant part of your body. Your results will either come back as “low risk” or “high risk.”
Prosigna. Doctors may use this test if you’ve already gone through menopause and you have invasive breast cancers that are hormone receptor-positive and HER2-negative. It classifies you as low, intermediate, or high risk. This test is for early-stage breast cancer that hasn’t spread to more than three lymph nodes.
Genomic Sequencing
If your cancer is advanced, or standard treatments aren’t working, your doctor may recommend genomic sequencing, also called next-generation sequencing (NGS) panels.
“In the metastatic setting, what we want to do is find specific vulnerabilities at the DNA level so we can use targeted therapies,” says Mouabbi. “So we do something called genomic sequencing.”
These tests can tell your doctor if you have BRCA1 or BRCA2, but they can also search for other mutations that can be treated with targeted therapies. Common examples include:
PIK3CA mutations. Up to 50% of breast cancers have this mutation. If you have it, your cancer may respond well to phosphoinositide 3-kinase (PI3K) inhibitors.
ESR1 mutations. ESR1 mutations cause breast cancer cells that “feed themselves” without hormones. This means hormone therapy won’t work as well for you. If a test shows you have changes in this estrogen receptor, you’re a good candidate for special drugs that could treat your cancer.
Some specific tests include:
FoundationOne CDx. This test requires a small amount of cancer tissue. It goes to a lab, where they test for variations (changes from the norm) in 324 different genes. This helps match you to a specific drug or therapy for your cancer.
Tempus. This checks for 648 cancer-related genes in your tumor tissue or blood using a matched normal sample as a reference.
Molecular Testing Advancements
There are new tests, such as circulating tumor DNA (ctDNA) assays, that can detect tiny traces of cancer DNA in your blood even before doctors can see it on scans.
Two examples include:
Signatera. A blood and tumor tissue test that can find trace amounts of cancer DNA in your bloodstream.
Guardant360. A blood-only liquid biopsy that shows your unique gene mutations.
“Because of this type of test, you can detect cancer coming back years before you can even see it,” says Mouabbi. “It can detect one cancer DNA out of a million healthy DNA.”
This means, he says, that recurring cancer can be caught earlier — when it’s most treatable. But you need to ask your doctor for these tests, which Mouabbi encourages.
Availability and Cost
Molecular diagnostics for breast cancer are available at specialized medical centers and hospitals across the U.S., including some academic centers. Your doctor can help point you to the nearest testing center. Most of these tests are covered by health insurance, says Mouabbi.
“If they’re not covered, the companies (may) run the test without billing (you)," he says, "But you have to be your own advocate. Unless you ask, you won’t know.”
A recent study found almost 25% of oncologists didn't talk to their patients about cost when discussing molecular testing. Check with your insurance provider to see what your plan covers, what it doesn't, and what your cost will be. Without insurance coverage or cost waivers, your out of pocket costs for breast cancer molecular testing may range from $200 for simple tests to $10,000 for more complex ones.
