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.

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.

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.

Currently, liquid biopsies are routinely done only on people diagnosed with metastatic breast cancer. Liquid biopsies look for circulating tumor DNA, also called ctDNA. Circulating tumor DNA are fragments of the cancer cells’ DNA that enter the bloodstream.

By analyzing the 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.

Right now, doctors don’t use 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.

“That 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.”

Liquid biopsies also can find circulating tumor cells, also called CTCs. Circulating tumor cells are cancer cells that have broken away from the cancer tumor and moved into the bloodstream. CTCs are important because they are the cells that cause recurrence and metastatic disease. They move throughout the bloodstream, interacting with other cells and eventually forming a tumor in a place away from the breast.

Researchers are actively studying how finding these molecules 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.

Research suggests that the number of CTCs is very small, as few as one cell in 10,000,000 white cells per 10 mL of blood. The challenge with circulating tumor cells is that while tests can detect them, there is no way to know when they will form a metastatic tumor. It could be five years, it could be 25 years. There is also no way to know where in the body the tumor will be. And until someone has a detectable tumor or symptoms, no doctor would recommend treatment because the side effects would greatly outweigh any benefits.

“Liquid biopsy for early-stage breast cancer is a very interesting research area,” Fox said. “But liquid biopsy should not be done in every-day practice for this type of breast cancer. What do you do if you find them? 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.”

Liquid biopsy tests can find ctDNA in people with early-stage disease. This is also an area of active research, because like circulating tumor cells, ctDNA can lead to a recurrence and metastatic disease. But also similarly, if ctDNA is found in someone who doesn’t have a recurrence or metastatic disease, it’s unclear what doctors should do. One ctDNA test you may hear about is called Signatera. This test, which is covered by Medicare for people with stage II or higher breast cancer, can help detect if cancer remains in the body after treatment.

In a 2024 review article in npj Breast Cancer, researchers said that ctDNA tests in early-stage breast cancer are a promising tool for screening, evaluating how effective a treatment is, and monitoring any residual disease. Residual disease is very small spots of cancer or individual cancer cells that may be left behind after surgery, chemotherapy, radiation, and other primary treatments.

But they pointed out that questions remain about how to select people who would most benefit from the tests, when the tests should be done, and the accuracy and reliability of the tests.

The U.S. Food and Drug Administration (FDA) has approved several liquid biopsy tests for people with metastatic breast cancer:

• Sponsor Message

  The Guardant360 test finds a number of mutations in ctDNA, including AKT1, BRCA1, BRCA2, ERBB2, ESR1, PALB2, PIK3CA, and PTEN.

• Sponsor Message

  The FoundationOne Liquid CDx test also finds a number of mutations i, including AKT1, BRCA1, BRCA2, ERBB2, ESR1, PALB2, PIK3CA, and PTEN.

• Sponsor Message

  The CellSearch test finds circulating tumor cells.

• Sponsor Message

  The MI Cancer SEEK test finds PIK3CA mutations.

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.

If your doctor recommends one of the FDA-approved tests, 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.