Liquid Biopsy: What Is It and When Is It Used in Breast Cancer?
In the future, researchers hope a liquid biopsy test may be able to detect cancer or other diseases with a minimally invasive procedure: a blood draw. There are a number of studies looking at liquid biopsies for breast cancer. But right now, they’re only regularly used for metastatic breast cancer.
What is a liquid biopsy test?
Essentially, a liquid biopsy is a blood test. When done on someone with breast cancer, a liquid biopsy analyzes a sample of blood and looks for cancer cells, cancer DNA or RNA, or other particles released by cancer cells that have travelled into the bloodstream. All the particles a liquid biopsy finds are considered biomarkers, molecules that are a sign of a disease.
How is a liquid biopsy different from a tissue biopsy?
A liquid biopsy is much less invasive than a traditional tissue biopsy. During a tissue biopsy, your doctor removes a sample of the cancer tumor, which requires either local or general anesthesia, one or more incisions, stitches, and recovery. The tumor sample undergoes a number of tests in a lab.
A liquid biopsy is a simple blood draw, done in a doctor’s office or lab facility.
When are liquid biopsies used for breast cancer?
Currently, liquid biopsies are routinely done only on people diagnosed with metastatic breast cancer, but may be done on people with early-stage disease in some cases. The type of liquid biopsy used is called a molecular residual disease (MRD) test. MRD tests look for circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs). Circulating tumor DNA are fragments of the cancer cells’ DNA that enter the bloodstream. CTCs are cancer cells that have broken away from the cancer tumor and moved into the bloodstream.
By analyzing the CTCs and ctDNA, doctors can see if certain genetic mutations are in the cancer cells, such as ESR1, AKT1, PTEN, BRCA1/2, or PIK3CA mutations. Knowing if the metastatic breast cancer has one of these mutations allows doctors to recommend medicines that target these mutations, including Orserdu (chemical name: elacestrant), Truqap (chemical name: capivasertib), Piqray (chemical name: alpelisib), Lynparza (chemical name: olaparib), or Talzenna (chemical name: talazoparib).
A tissue biopsy is also usually done on metastatic breast cancer to determine the hormone receptor status and HER2 status of the cancer. And though tissue biopsies also can provide information on genetic mutations in the cancer, getting this information from the removed tissue takes much longer than getting it from a liquid biopsy blood test.
Can liquid biopsies show if a metastatic treatment is working?
Right now, doctors don’t use only liquid biopsies to determine if metastatic breast is responding to treatment, according to Kevin Fox, MD, professor emeritus of medicine at the University of Pennsylvania, a medical oncologist who specialized in the treatment of breast cancer. Fox also is a Breastcancer.org medical adviser.
“The use of liquid biopsy to determine the effectiveness of a treatment for metastatic breast cancer is being studied, but we’re not there yet,” Fox explained. “We need imaging to see if a treatment is working. We need to see if the cancer is shrinking or staying stable.”
Research on liquid biopsy for early-stage breast cancer
If a liquid biopsy finds ctDNA or CTCs after treatment for early-stage breast cancer, it may mean that the cancer is coming back (recurrence).
The challenge with CTCs and ctDNA in early-stage disease is that while tests can detect them, there is no way to know when they will cause a recurrence. It could be five years, 25 years, or never. There’s also no way to know where in the body the cancer will return. Until someone has a detectable tumor or symptoms, no doctor would recommend treatment because the side effects would greatly outweigh any benefits.
Researchers are actively studying how detecting CTCs and ctDNA via liquid biopsy in people with early-stage breast cancer can help inform treatment decisions and possibly assist in determining prognosis. Still, liquid biopsies are not routinely used on early-stage disease outside of clinical trials.
“Liquid biopsy for early-stage breast cancer is a very interesting research area,” Fox said. “But liquid biopsy should not be done in everyday practice for this type of breast cancer. What do you do if you find [CTCs or ctDNA]? There’s nothing you can do because the patient doesn’t have a lump or lesion yet. It would be unethical to treat them. So there is nothing the patient can do but worry.”
FDA-approved liquid biopsy tests used for breast cancer
The U.S. Food and Drug Administration (FDA) has approved several liquid biopsy tests for people with metastatic breast cancer:
The Guardant360 test finds a number of mutations in ctDNA, including AKT1, BRCA1, BRCA2, ERBB2, ESR1, PALB2, PIK3CA, and PTEN.
The FoundationOne Liquid CDx test also finds a number of mutations in ctDNA, including AKT1, BRCA1, BRCA2, ERBB2, ESR1, PALB2, PIK3CA, and PTEN.
The CellSearch test finds circulating tumor cells.
The MI Cancer SEEK test finds PIK3CA mutations.
Other liquid biopsy tests used for breast cancer
There are a number of MRD tests available for breast cancer. The Signatera test is the most well known.
Cost and insurance coverage of liquid biopsy tests
The cost of liquid biopsy tests vary depending on a number of factors, including which test you have, what the test is looking for, and your insurance coverage.
All the FDA-approved liquid biopsy tests are covered by many health insurance plans, including Medicare, as well as Medicaid in some states.
The Signatera test is covered by Medicare and many insurance plans.
If your doctor recommends a liquid biopsy test, it makes sense to check with your insurance company about your coverage and any co-pays you might have. If the cost of the liquid biopsy isn’t covered or you can’t afford the co-pay, many of the companies that make the tests have patient assistance programs available through their websites.