Circulating tumor DNA (ctDNA) tests

Circulating tumor DNA (ctDNA) tests are blood tests that look for pieces of genetic information (DNA) that break away from tumors and enter the bloodstream. In the past, it was only possible to look for this genetic information after performing a needle or surgical biopsy to remove a sample of cancerous tissue.

Cancer cells have specific gene changes (mutations) that normal cells do not. Checking the blood for mutations or other kinds of gene changes can help doctors understand:

• Whether an early-stage breast cancer is coming back (recurring)
• How well a breast cancer treatment is working
• If metastatic breast cancer (breast cancer that has spread to other parts of the body) is growing
• If metastatic breast cancer has gene mutations or other gene changes that can be matched to a treatment

ctDNA tests are a type of liquid biopsy: a blood test that can look at cancer cell DNA without needing a surgical or needle biopsy.

Below, we’ll talk more about the different types of ctDNA tests, what we know and don’t yet know about their benefits, and how to talk with your doctor about whether ctDNA testing might be helpful for you.

Types of ctDNA tests

ctDNA tests can find tumor cell gene mutations in the blood. Different types of ctDNA tests can use the results in different ways:

• Some ctDNA tests check the blood for tumor cell gene mutations that can be matched to a treatment. These tests are used regularly in metastatic breast cancer.
• Other ctDNA tests check the blood for tumor cell gene mutations to help confirm that there are small amounts of cancer growth that are too tiny to be seen on a scan. This is called minimal residual disease, or MRD. ctDNA MRD tests are still being studied, but some doctors are using them now in certain people with breast cancer. For example, MRD tests may be helpful to see if metastatic breast cancer has grown or is responding to treatment.

Below, you can read more about each type of ctDNA test.

ctDNA tests that match a cancer to a treatment

ctDNA tests are not currently used to match early-stage breast cancer to specific treatments. But they are used regularly to help match metastatic breast cancers to treatments.

ctDNA tests look for gene changes, called mutations, that develop in metastatic breast cancer cells. These are sometimes called somatic mutations.

• Somatic mutations develop over time in cells after a person is born.
• It’s important to know that ctDNA tests that look for somatic mutations are different than blood tests to check for inherited mutations that run in families, such as BRCA1 and BRCA2.

Right now, treatments can’t be matched to every known mutation found in a ctDNA test. But several treatments can be:

• Elacestrant (Orserdu) is a treatment for hormone receptor-positive, HER2-negative metastatic breast cancer that has a mutation in a gene called ESR1.
• Imlunestrant (Inluriyo) is another treatment for hormone receptor-positive, HER2-negative metastatic breast cancer with an ESR1 mutation.
• Alpelisib (Piqray) is a treatment for hormone receptor-positive, HER2-negative metastatic breast cancer that has a mutation in a gene called PIK3CA.
• Inavolisib (Itovebi) is a treatment for hormone receptor-positive, HER2-negative metastatic breast cancer that has a PIK3CA mutation.
• Capivasertib (Truqap) is a treatment for hormone receptor-positive, HER2-negative metastatic breast cancer that has one or more mutations in genes called PIK3CA, AKT1, and/or PTEN.
• Entrectinib (Rozlytrek) is a treatment for tumors with an NTRK fusion, meaning that the gene NTRK is abnormally joined to another gene.

Visit the Biomarker testing page to learn more about the gene mutations and other gene changes mentioned above.

If you have been diagnosed with metastatic breast cancer, ask your care team about ctDNA testing at the time of diagnosis or if the cancer grows and you are considering a new treatment.

ctDNA tests use different technologies to find mutations that can be matched to treatment:

• Next-generation sequencing (NGS) can look at hundreds of mutations at a time.
• Polymerase chain reaction (PCR) can look for certain, specific mutations.

What the research shows

Research has proven that ctDNA testing can work well to match advanced and metastatic breast cancers to effective treatments.

The SERENA-6 clinical trial studied people with advanced estrogen receptor-positive breast cancer. The people were being treated with aromatase inhibitor hormonal therapy plus a CDK4/6 inhibitor such as abemaciclib (Verzenio), palbociclib (Ibrance), or ribociclib (Kisqali). This is considered to be standard treatment for this diagnosis.

Researchers used ctDNA testing to see if a new ESR1 mutation developed in the cancer cells.

People with cancer that developed a new ESR1 mutation were randomly assigned to two different groups:

• One group switched from an aromatase inhibitor plus a CDK4/6 inhibitor to a new hormonal therapy called camizestrant plus a CDK4/6 inhibitor.
• The other group continued standard treatment with an aromatase inhibitor plus a CDK4/6 inhibitor.

For the group who switched to camizestrant based on the ctDNA test result, cancer stopped growing and spreading (progressing) for about 7 months longer than it did for the other group. Camizestrant is expected to be FDA approved to treat metastatic breast cancer in 2026.

ctDNA tests have also been used to detect mutations in other advanced and metastatic breast cancer treatment studies, including studies of elacestrant and inavolisib.

Right now, there is not enough evidence to support using ctDNA tests to select treatment in early-stage breast cancer. This is because the amount of ctDNA in the blood of people with early-stage breast cancer may be too low for current technology.

Paying for ctDNA tests that match a cancer to a treatment

Health insurers often cover ctDNA tests that look for metastatic breast cancer gene mutations and other biomarkers that can be matched to a treatment.

Learn more about paying for this type of ctDNA test.

ctDNA tests for minimal residual disease (MRD)

ctDNA tests can also detect the presence of minimal residual disease, also called microscopic residual disease or MRD. These are tiny amounts of cancer that are much too small to show up on imaging tests, such as MRI or CT scans.

ctDNA tests for MRD are being studied in early-stage and metastatic breast cancer. Right now, these tests are not considered to be part of standard care according to guidelines issued by organizations such as the National Comprehensive Cancer Network and the American Society of Clinical Oncology.

Still, in some cases, people and their doctors may decide that MRD tests are helpful for their situations.

How ctDNA-based tests for MRD can be used

Right now, doctors use the following tests to monitor for breast cancer recurrence and treatment response:

• Physical exams
• Imaging scans
• Testing for biomarkers such as CEA protein levels. High levels of CEA can mean that cancer is present in the body.

Even with these tests, it’s still difficult to predict which cancers are more likely to recur and could benefit from more intensive treatment. For example, up to 30% of people with early-stage cancer will eventually have a recurrence after treatment.

Researchers are interested in MRD ctDNA tests because knowing whether small amounts of cancer are present could provide information that existing tests can’t. It’s important to know that MRD testing may be useful in addition to other tests, like scans, and not instead of other tests.

ctDNA tests for MRD are being studied for several uses:

• In early-stage and metastatic breast cancer, MRD tests could be used to find out if the cancer is responding to treatment.
• In early-stage breast cancer, the results may help predict the likelihood of later recurrence after treatment. Knowing that there are small amounts of cancer cells in the body indicates a higher risk of the cancer coming back.
• These tests can detect recurrence before a scan can. However, doctors don’t yet know if this information can be used to guide treatment changes in a way that helps people.

MRD testing has shown promise in colorectal, lung, urothelial (urinary system), and breast cancers. While these tests are not yet considered part of standard care for breast cancer, that could change as more research is done.

Doctors may decide to use these tests in some people with breast cancer on a case-by-case basis.

How ctDNA-based MRD tests work

A blood sample from someone with breast cancer often contains DNA from a mixture of sources—healthy cells and cancer cells.

Breast cancer cell DNA contains gene mutations and other changes common in breast cancer and unique to the person’s tumor. DNA from normal cells doesn’t have these mutations. If MRD testing finds breast cancer-related mutations in the blood, it means breast cancer cells are present somewhere in the body.

These mutations can be found with ctDNA-based MRD tests that use PCR or next-generation sequencing technology.

MRD blood tests are typically done every 3-6 months to track whether ctDNA is present.

Types of ctDNA-based MRD tests

There are two main types of MRD ctDNA tests—personalized tests and tumor-naïve tests.

Personalized tests (also called tumor-informed)

• For these ctDNA tests, a sample of the tumor tissue is analyzed first to find specific gene mutations in the tumor tissue. This requires a biopsy. Sometimes, tissue from a previous biopsy can be used.
• The mutations found are then used to create the blood test.
• It can take up to 1 month to analyze the tissue and create the test.
• After the test is ready and your blood is drawn, the results usually come back in 1 to 2 weeks.
• Every time the blood test is given, it looks for the tumor’s unique cancer cell gene mutations to confirm whether cancer is present or absent.

An advantage: They can look for the mutations that are unique to an individual tumor. This helps the test find even very low levels of MRD.

Disadvantages:

• It requires a tumor sample.
• It takes time to create the test and get the first results.
• Personalized tests can’t detect new mutations that may arise over time.
• These tests can be more expensive than tumor-naïve tests, although in some cases they are covered by insurance and/or cost savings programs.

Tumor-naïve tests

• These tests are not personalized to the tumor, so they don’t require a tissue sample. Instead, they test the blood for gene mutations and other changes commonly associated with breast cancer.
• Results usually come back in 1 to 2 weeks.

Advantages:

• No tumor sample is needed.
• First results arrive faster than personalized test results because there’s no wait time to create the test.
• Tumor-naïve tests cost less than personalized tests.

A disadvantage: This type of test does not detect mutations specific to an individual tumor.

“To create a personalized ctDNA-based MRD test, the testing company examines most or all of the tumor tissue DNA. This creates a unique barcode of that specific cancer in that specific person,” says Pallav Mehta, MD, medical oncologist at MD Anderson Cancer Center at Cooper. “Then, the test scans the vials of blood and sounds an alarm if even a piece of that barcode is found. The tumor-naive testing already comes with a preset list of barcodes that are commonly found in cancers and simply scans the blood for those.”

Several companies make ctDNA-based MRD tests. The tests below are being used or studied in breast cancer. This is not a complete list:

• Guardant Health’s Guardant Reveal test is a tumor-naïve test for early-stage cancer. It can monitor for recurrence.
• Exact Sciences’ Oncodetect is a personalized test. The test can monitor therapy response and risk of recurrence. The test result is “positive” or “negative,” and it also measures the amount of ctDNA.
• Invitae’s Personalized Cancer Monitoring Test is a personalized test. The result is “detected” or “not detected.”
• Natera’s Signatera test is a personalized test for stage IIB and higher breast cancer. The test can monitor therapy response and recurrence. The test result is “positive” or “negative,” and it also measures the amount of ctDNA. The amount of ctDNA may provide information on whether cancer may be growing or if it is responding to treatment.
• SAGA Diagnostics’ Pathlight test is a personalized test that monitors for recurrence in stage II and III breast cancer.

Different cancer centers may use different ctDNA-based MRD tests. If you and your doctor decide that MRD testing would be helpful for you, the kind of test used may depend on where you receive your care.

What ctDNA-based MRD test results mean

MRD test results, whether from a personalized or tumor-naïve test, are “positive” or “negative”:

• Positive means that the blood sample contains DNA with mutations (from cancer cells) and DNA without mutations (from normal cells). Positive also means that there is cancer in the body.
• Negative means that the blood contains only DNA without mutations and that there is no evidence of cancer.

In MRD testing studies of people with early-stage breast cancer:

• A positive MRD ctDNA test result accurately predicts eventual recurrence of breast cancer.
• A negative result suggests that the risk of recurrence is low.

In metastatic breast cancer: Some MRD tests also measure the amount of ctDNA in the sample. Knowing the amount of ctDNA may be helpful for people with a known diagnosis of metastatic breast cancer because:

• Increasing levels of ctDNA over time could mean that cancer is growing and could detect metastasis before it is seen on a scan or causes a symptom.
• Decreasing levels could mean that cancer is responding to treatment.

It’s important to know that a negative MRD ctDNA result is not a reason to go without treatments or stop them earlier than recommended.

Potential uses in early-stage breast cancer

In early-stage breast cancer, MRD ctDNA testing is being studied to see if it can be used to monitor how the cancer is responding to treatment; to monitor for recurrence after treatment is finished; and to tell doctors that treatment needs to be changed or restarted. The hope is that the presence of ctDNA can tell doctors sooner than a scan that cancer is coming back and that it is time to change or restart treatment.

After neoadjuvant therapy (treatment given before surgery), MRD ctDNA testing may be a way to:

• Find out if any cancer is still present
• Predict recurrence and survival
• Predict a complete response in high-risk breast cancer

After surgery, this testing can be used to inform decisions about the treatment plan moving forward by answering questions such as:

• Does this cancer have a high or low risk of recurrence?
• Does the cancer need more or less treatment?

During treatments after surgery, such as chemotherapy or targeted therapies, MRD ctDNA may help to find out how well the cancer is responding.

Clinical trials are testing how useful ctDNA MRD testing is in people with early-stage breast cancer.

What the research shows so far

The Exploratory Breast Lead Interval Study (EBLIS), published in 2024, used Signatera to monitor people with early-stage breast cancer every 6 months after surgery. A positive test result predicted eventual recurrence as much as 3 years before any cancer showed up on imaging scans.

As reported in 2023, another trial that used Signatera, called I-SPY2, found that a negative ctDNA result after the first treatment given before surgery (neoadjuvant treatment) was a good indicator that the cancer would respond completely to treatment. The study also showed that:

• Of people who still had evidence of disease but a negative ctDNA result after a few treatments, most remained free of metastatic recurrence.
• People with positive ctDNA test results had a higher risk of metastatic recurrence later on.

A study published in 2025 showed that the Invitae Personalized Cancer Monitoring test detected ctDNA in people with high-risk breast cancer almost a year before their recurrence was detected through scans and other tests.

A study presented at the San Antonio Breast Cancer Symposium in 2023 that used the Guardant Reveal test showed that ctDNA was detected 7.9 months before a recurrence in people with early-stage breast cancer.

Potential uses in metastatic breast cancer

Most people with metastatic breast cancer will have a positive MRD ctDNA test, because cancer cells are known to be present in one or more areas of the body.

However, tests that measure changing MRD ctDNA levels could help your doctor see how well the cancer is responding to treatment. While this use is not standard of care, some doctors may decide to use these tests on a case-by-case basis:

• If ctDNA levels are falling, or they become undetectable in the blood, this would suggest that a treatment is working.
• If ctDNA levels are increasing, this may suggest that treatment is not controlling the cancer or that new sites of metastasis are developing.

In people with metastatic breast cancer, researchers are studying whether MRD testing can be used to:

• Monitor treatment response and predict survival
• Look for new mutations that can be matched to a treatment
• Guide the decision to change treatment

What the research shows so far

There are several ongoing trials studying ctDNA-based MRD tests in metastatic breast cancer.

For example, researchers are using Guardant Reveal in people with HER2-positive metastatic breast cancer to guide decisions about stopping anti-HER2 therapy if the breast cancer is well-controlled.

The test has shown good agreement with CT scans. Next, researchers are planning a trial called PHENIX to test whether using Guardant Reveal to detect MRD with can help guide decisions about stopping anti-HER2 therapy.

What researchers are still learning

Clinical trial researchers are working to learn more information about MRD ctDNA testing in breast cancer, such as:

• The risk of false-negative results that could cause doctors to miss cancer.
• The best course of action for a person who is being monitored with ctDNA testing and receives a positive result. A positive ctDNA test may suggest the need for more frequent monitoring, additional treatment, or watch and wait.
• The best type and timing of treatment to use after a positive ctDNA test result. Researchers need to learn if starting treatment sooner leads to better outcomes than waiting until cancer is visible on imaging scans.
• Whether people on a ctDNA-guided treatment plan do better than those who follow the current standard of care and are monitored with imaging scans, physical exams, and CEA blood level testing.
• How long to continue regular ctDNA-based MRD testing. It’s not known how long ctDNA testing should continue if scans suggest that a person treated for early-stage breast cancer remains cancer-free for a certain number of years.
• How reliable ctDNA tests are at predicting response to treatment and recurrence risk.

If you have questions about whether ctDNA-based MRD testing would be helpful for you, talk with your care team about the pros and cons of testing.

Pros and cons: talking with your doctor

Although MRD ctDNA testing is not part of current evidence-based guidelines, some doctors may decide to use these tests in combination with other tools, such as imaging scans and biomarker testing.

If you and your doctor are considering MRD-based ctDNA testing, it’s important to talk about potential pros and cons.

Your doctor can help you understand the value of ctDNA testing for your individual situation. Think about how you might react to any results you receive, and how this may affect your daily life.

You can also:

• Ask your doctor about enrolling in a clinical trial that is studying MRD ctDNA tests in people with breast cancer.
• Search clinical trial databases using the term “ctDNA” or “MRD.”

Here are some of the potential pros and cons of testing:

Pros

For some people, MRD ctDNA testing may provide peace of mind if they’re concerned about recurrence. Potential advantages include:

• Having another piece of information to judge whether there is a small amount of cancer left behind after surgery or other treatments
• More accurate information about whether an early-stage cancer that appeared to be treated successfully is likely to recur later on
• Understanding whether metastatic disease is responding to treatment

Cons

At the same time, there are some disadvantages to testing.

It’s not yet known whether ctDNA tests are 100% accurate. A negative result may give a false sense of security, while a positive result may trigger high levels of anxiety.

• A negative result does not mean the cancer definitely will not come back.
• There is uncertainty about next steps after a positive MRD ctDNA result. Doctors don’t yet know whether more frequent imaging, more treatment, or changes in treatment will make a difference in outcomes. They also don’t know if there is a benefit to starting or restarting treatment before cancer shows up on imaging scans.
• A positive result could lead to overtreatment, with people experiencing difficult side effects from treatments that weren’t necessary.
• A negative result might tempt someone to discontinue a treatment with bothersome side effects too early—which could increase the risk of recurrence.
• Because these tests are not FDA approved, they might not be covered by health insurance. Some companies offer financial assistance for tests that aren’t covered.

Until clinical trials provide more information, it’s best to talk to your doctor about whether these tests may be useful for you.

Paying for ctDNA-based MRD testing

Some ctDNA-based MRD tests are covered by Medicare. Still, insurance may not always cover this kind of testing.

If you’ve been diagnosed with any stage of breast cancer and are interested in ctDNA MRD testing, talk with your doctor about whether it could be helpful.

Always call your insurance company to confirm if a test is covered.

To learn more about paying for care, visit the Financial matters page.