Navigating life after a cancer diagnosis can often feel like navigating a relentless series of unknowns.
SignateraTM, a molecular residual disease (MRD) test available for those diagnosed with solid tumor cancers, including breast, ovarian, and endometrial cancers, aims to reduce some of those unknowns through personalized monitoring that may identify a cancer recurrence or response to treatment earlier than methods in routine practice today.
The Breasties Guide to Molecular Residual Disease Testing with SignateraTM hopes to provide you with an overview of what you need to know about MRD testing.
Similar to cancer care, surveillance and monitoring should not be one-size-fits-all. While one Breastie may thrive with as much information as possible, additional testing may increase anxiety in others. Either way, you deserve to know all your options. Because when you know your options, you can play an active role in your cancer management and work with your medical team to personalize the best care for you.
Continue reading to learn more about MRD testing, how it differs from other forms of cancer testing, and how to navigate the test results. Shared decision-making reflection questions and conversation starters that you can use to determine if MRD testing is right for you.
Peak Partnered: This article was developed in partnership with Natera. Natera and The Breasties are joining forces to raise awareness about options for continued surveillance and monitoring after a cancer diagnosis.
Molecular Residual Disease Testing 101
Circulating tumor DNA, or ctDNA, refers to small fragments of tumor DNA shed from cancer cells. Tumor tissue-informed molecular residual disease (MRD) testing is a highly sensitive blood test that can detect those fragments.
Think of it like the lint that collects in your dryer while doing laundry. If you look closely when you clean out the lint trap, you can sometimes identify what article of clothing certain bits of lint came from, like a bright blue thread from your favourite sweater or green fluff from a comfy pair of socks.
Tissue-informed MRD testing is similar. A lab creates a personalized test using tissue samples from your specific tumor and normal blood cells, representing your “normal” non-cancer state. If the test is positive, it means ctDNA was detected in the blood sample, which tells you that there may be cancer cells somewhere in your body that are shedding fragments of tumor DNA into your bloodstream.
Because this testing happens at the cellular level, cancer can be identified in the body months before traditional imaging studies like a PET scan or MRI. For some, this can create a catch-22. That’s because definitive guidelines for how to treat cancer that has yet to re-appear on a scan await the results of research studies that are underway. Even so, tests like these can alert us to look closer and be more diligent during surveillance or treatment decision-making, if deemed appropriate.
It is also important to note that MRD testing reflects your health at a specific moment in time: when your blood was drawn. That is why MRD testing is often repeated. Seeing how the test results change over time can help identify if your cancer has returned after being undetectable and/or monitor the efficacy of your treatment.
While researchers continue to learn more about how and why cancers recur after treatment, Dr. Angel Rodriguez, Senior Medical Director at Natera, explained that physicians are in a tough spot.
“We can’t seem to accurately identify who is at risk [of their cancer progressing] so that we can then intervene earlier,” he said.
“Outside of routine surveillance”, he continued, “most cancer survivors are told to alert their medical team if they have any concerning new symptoms that could be indicative of a recurrence.”
The hope is that emerging technologies, like MRD testing, will enable physicians to identify a recurrence or progression before symptoms arise.
Understanding ctDNA Test Types: Tissue-Informed vs Tissue-Naive
There are different approaches to ctDNA testing: tissue-informed and tissue-naive.
As mentioned earlier, tissue-informed tests are personalized because they are created using DNA from your original tumor. This is what makes those tests highly sensitive, allowing them to track the disease over time.
Tissue-naive testing does not require a sample of the tumor. While these tests are not personalized, they can still play an important role in surveillance and monitoring.
Unlike tissue-informed testing, tissue-naive tests are based on a pre-selected panel of general cancer-associated DNA changes, as opposed to DNA from your unique tumor. As a result, they may be associated with more false positive results, or might miss low levels of ctDNA.
Tissue-naive tests can play an important role because adequate tumor tissue is not always available. That could be a result of biopsy tissue being limited or chemotherapy causing changes to the tumor that affect testable tissue, for example. A lack or limited amount of tissue can make it more challenging to develop a personalized test. If that’s the case, a tissue-naive ctDNA test may be an appropriate alternative.
MRD vs Other Biomarker Tests
I can hear you yelling: “Wait! Doesn’t my team already use blood tests to monitor cancer?”
And yes, they might. Many people impacted by breast and gynecologic cancers are already monitored with tumor markers, which are proteins found in the bloodstream.
Natera’s Chief Medical Officer, Dr. Minetta Liu explained that these proteins, like ctDNA, are also shed by tumor cells. However, these proteins are not unique to the person or the cancer. They can come from other sources under non-cancerous conditions or increase in response to other things happening in the body, like an infection.
Because of those limitations, a rise in the tumor marker level does not definitively mean that a cancer has recurred or that a new cancer has developed. Current data suggest that tumor marker levels are not accurate as serial ctDNA testing, which is much more specific to one’s cancer.
Navigating MRD Testing Results with Signatera
A negative test result means ctDNA was not detected in your blood at the time of blood collection. While this is generally a good sign, it is not a guarantee that the cancer is fully gone or won’t return.
A positive test result means that ctDNA was found in your blood, which could mean that some cancer cells are still present, that the cancer has recurred, and/or that your treatment may need to be adjusted or monitored more closely.
Your care team may recommend additional tests or imaging to follow up on a positive test result, using the trend in the amount detected to inform next steps.
You may also receive a TNP, or Test Not Performed result, which means the test could not be completed. That could be because there was not enough DNA to run the rest or your sample didn’t meet quality standards. The report will explain why you received a TNP and your doctor may ask you to repeat the test.
Use of Molecular Residual Disease Testing
Molecular Residual Disease (MRD) testing is not yet part of the standard of care for breast cancer or all types of gynecologic cancers, as determined by guidelines from the National Comprehensive Cancer Network (NCCN) or American Society of Clinical Oncology (ASCO). In 2022, the NCCN added ctDNA testing to its guidelines for cervical cancer, suggesting its use to create a detailed analysis of the cancer’s full genetic makeup when tissue samples are unavailable.
As a result, the use of MRD testing is largely based on preference and shared decision-making between a patient and their doctor.
What Does the Research Say?
Research involving MRD testing in breast and gynecologic cancers is ongoing, with many studies looking to understand who may benefit from intensified surveillance and how MRD testing results can be used to help inform therapeutic decisions.
In breast cancer, the PREDICT-DNA trial, which published its findings in March 2026, found that ctDNA testing may help understand who is at higher risk for recurrence. The study found that those who were ctDNA-negative after chemotherapy and before surgery, regardless if they achieved pathological complete response (PCR), were less likely to experience a recurrence.
Similar results have been found in the I-SPY 2 trial. Results published in December 2025 showed that ctDNA testing can help identify which breast cancer patients are at a low risk of metastatic recurrence, even without a pCR to chemotherapy before surgery. This information enables the multidisciplinary care team to make informed, risk-based recommendations on subsequent management.
Research on or involving the application of ctDNA testing in ovarian and endometrial cancers is also ongoing, largely focused on treatment monitoring. Because ctDNA is more precise than protein biomarker testing, researchers have found that ctDNA may be more effective than CA-125 testing at identifying early recurrences of epithelial ovarian cancer.
Understanding if MRD Testing is Right For You
Self-Reflection Questions
Survivorship and thrivership are not one-size-fits-all, and there are many options for follow-up or maintenance care, based on personal needs and preferences. For many, a regular, minimally-invasive blood test like Signatera can provide a sense of control and empowerment, rather than just waiting for the next scan.
Below are some questions that you can use to decide if MRD testing might be right for you:
- How satisfied are you with your current cancer surveillance and follow-up care?
- How do you feel while waiting for test results? Do you experience anxiety while waiting for results from scans and/or bloodwork, or does the knowledge that information is coming provide you with peace of mind?
- How comfortable are you in speaking with your medical team when you have questions about imaging or test results?
- What tools or support system do you have to help navigate feelings of discomfort and anxiety related to cancer?
Conversation Starters for You and Your Team
- How often should I repeat MRD testing?
- How might MRD testing help me navigate feelings of uncertainty around my risk of recurrence or progression?
- How will my test results inform my treatment and/or monitoring strategy?
- What would a negative test mean for my treatment/monitoring? What about a positive test?
- Where can I access the most up-to-date information about ctDNA?
Frequently Asked Questions
My doctor says they wouldn’t be able to act on a positive test result. Why is that? What if I’d like to get MRD testing anyway?
Research is ongoing to understand ways that MRD test results can be used to guide cancer treatment. This research is essential and can inform future guidelines.
As Natera’s senior medical director Angel Rodriguez, MD explained, a physician ordering a test wants to know how the information gained from that test will be used, and, in the absence of guidelines, there may be uncertainty about how your test results can be applied.
If you feel strongly that MRD testing is right for you, Dr. Rodriguez encourages you to have intentional discussions with your care team to engage in shared decision-making: explain why you would like this information, ask to hear their concerns, and share what you’ve learned so that you can be on the same page.
Will my insurance cover Signatera MRD testing?
Signatera is covered by Medicare for monitoring disease progression, disease recurrence, and/or disease relapse in people who have been diagnosed with:
- Stage 2 to 4 breast cancer with chemotherapy before surgery, regardless of subtype
- Stage 2b and higher breast cancer with chemotherapy after surgery and recurrence monitoring settings
- Stage 2 to 4 ovarian, fallopian tube, or primary peritoneal cancer in the adjuvant and recurrence monitoring settings
Natera recommends that you call your insurance provider beforehand to confirm coverage for the specific MRD test and to ask about costs, including any potential out-of-pocket costs, co-pays, or deductibles.
Natera’s Patient Support team can also assist with benefit verification, and their Financial Assistance Program can also provide information.
