Signatera and Other MRD Tests for Breast Cancer

Signatera is a type of test called a molecular residual disease (MRD) test. It looks for bits of a cancer tumor in your blood, specifically circulating tumor DNA (ctDNA). ctDNA is a cancer tumor marker, which is a molecule that is a sign of a disease.

Signatera and other MRD tests are types of liquid biopsies.

The Signatera test involves two steps. First, the test analyzes a cancer tumor sample that’s been surgically removed, looking for genetic mutations specific to that particular cancer. Then the test looks for these mutations in DNA in a sample of your blood.

Cancer tumors have genetic mutations that aren’t in the rest of your cells. If the cancer’s mutations are found in your blood sample, it means that ctDNA has broken away from the cancer and is travelling through your body.

The Signatera test can assess how well stage II and stage III breast cancer is responding to treatments given before surgery (called neoadjuvant treatments by doctors), which can help estimate the risk of recurrence (the cancer coming back).

The test is also used to determine how well stage IV, or metastatic, breast cancer is responding to treatment.

Signatera test results say whether ctDNA was found in the blood sample. This is reported as positive (ctDNA was found) or negative (ctDNA wasn’t found).

The results will also tell you the amount of ctDNA in the blood sample. This is often reported as the mean (average) tumor molecules per milliliter of blood or MTM/mL.

A negative Signatera result means that the test didn’t detect ctDNA. This means the risk of recurrence of early-stage breast cancer is low. If the cancer is metastatic and the first Signatera test found ctDNA in your blood, but then the test was repeated and the results were negative, it means the cancer is responding well to treatment.

A positive Signatera test result means different things depending on whether the breast cancer is early-stage or metastatic.

Positive Signatera result for early-stage breast cancer

If the breast cancer is early-stage, a positive Signatera test means that the cancer may possibly come back, either in the breast area or in a part of the body away from the breast. If you’re deciding on treatments after surgery, you and your doctor may decide on more aggressive treatments to lower this risk of recurrence.

If you get positive test results after you’ve completed treatment, deciding what to do is more challenging. While the Signatera test can detect ctDNA, there’s no way to know if and when a recurrence will happen. It could be five years, it could be 25 years, or it could be never. There’s also no way to know where in the body the cancer will come back. And until a person has symptoms or a tumor that can be seen on a mammogram or another imaging test, doctors probably won’t recommend treatment because the side effects of treatment would greatly outweigh any benefits.

For this reason, some people find a positive Signatera test after treatment for early-stage breast cancer frustrating and anxiety-provoking. This is also why liquid biopsy tests like Signatera aren't routinely used on early-stage disease outside of clinical trials. Research on how best to proceed after a positive Signatera result in this situation is ongoing.

Positive Signatera result for metastatic breast cancer

If the breast cancer is metastatic, a positive Signatera result may mean that the tumor is growing, especially if the amount of ctDNA increases over time. Your doctor likely will order imaging tests to confirm the result. If the tumor is growing, your doctor will probably recommend changing your treatment plan or adding one or more medicines to the regimen. How best to use Signatera results in metastatic breast cancer is also an area of active research.

False positives and false negatives

Natera, the company that makes the Signatera test, says the test is 98–99% accurate, so the risk of false-positive or false-negative results is small. Still, they can happen.

A false-positive result means the test says ctDNA has been detected, but isn’t really there. This can happen because a very low level of ctDNA can cause a positive result, but then the ctDNA is cleared by the body.

If you’ve been diagnosed with metastatic disease, your doctor will almost always recommend imaging tests to confirm the finding and may recommend another Signatera test in four to eight weeks. If you have early-stage disease, your doctor may recommend imaging and may recommend another Signatera test.

A false-negative result means the test says there’s no ctDNA in your blood, but the cancer particles are there or the cancer has grown or recurred. This can occur because the blood sample didn’t happen to contain any ctDNA. It can also happen because a new cancer tumor isn’t shedding any ctDNA into the bloodstream.

The Signatera test is covered by Medicare and many insurance plans. The cost varies depending on your diagnosis and your specific health insurance. If your doctor recommends the Signatera test, it makes sense to check with your insurance company about your coverage and any co-pays you might have. If the test isn’t covered or you can’t afford the co-pay, there’s information about financial assistance and other support on the Signatera Billing page.

While the Signatera test is probably the most well known for breast cancer, there are other MRD tests available. Research is ongoing to develop new tests, so this list may not reflect all the currently available tests.

CellSearch

The CellSearch test can be used to assess how well metastatic breast cancer is responding to treatment by measuring circulating tumor cells (CTCs) rather than ctDNA. CTCs are cancer cells that have broken off from the tumor and are in the bloodstream.

Guardant Reveal

The Guardant Reveal test can be used to predict the risk of early-stage breast cancer coming back after surgery and may also help doctors decide if more treatments after surgery would help reduce the risk of recurrence.

Oncodetect

The Oncodetect test may be used to help figure out the risk of early-stage breast cancer coming back after surgery.

Precise MRD

The Precise MRD test may be used to predict the risk of early-stage breast cancer coming back after surgery. It may also help doctors decide if more treatments after surgery would help reduce the risk of recurrence.

FlexOMx Lab

The FlexOMx Lab test is currently only available for use in research.

Labcorp Plasma Detect ID MRD

The Labcorp Plasma Detect ID MRD test may be used to predict the risk of early-stage breast cancer coming back after surgery.

RaDar ST

The RaDar ST test may be used to help figure out if early-stage hormone receptor-positive HER2-negative breast cancer may come back after surgery and hormonal therapy.

NeXT Personal DX

The NeXT Personal DX test may be used to predict the risk of early-stage breast cancer coming back after surgery and other treatments.

Haystack MRD

The Haystack MRD test may be used to help figure out if early-stage breast cancer may come back after surgery and other treatments.