Editor’s Note: This article was developed from a podcast conversation and has been edited for clarity, readability, and length while preserving the original insights and intent of the discussion.
In recent months, many inflammatory breast cancer (IBC) patients have been asking the same question:
What does a Signatera result really mean?
As circulating tumor DNA (ctDNA) testing becomes more widely available, patients are increasingly hearing about blood tests that may help detect evidence of cancer at the molecular level. The excitement surrounding these tests is understandable. Patients want more information, earlier answers, and every possible advantage in monitoring their disease.
To help address some of the most common questions, Talk IBC recently hosted a discussion with Dr. Wendy Woodward, Executive Director of the Morgan Welch Inflammatory Breast Cancer Research Program and Clinic at MD Anderson Cancer Center, and Dr. Azadeh Nasrazadani, a breast medical oncologist specializing in IBC.
Their message was both hopeful and realistic: Signatera and similar tests show tremendous promise, but there is still much to learn before they become a standard guide for treatment decisions.
What Is Signatera?
Signatera is a personalized blood test designed to detect circulating tumor DNA, or ctDNA. These are tiny fragments of DNA that may be released into the bloodstream by cancer cells.
Unlike some blood-based cancer tests, Signatera is customized for each individual patient. A sample of the patient’s tumor is analyzed, and a personalized assay is created to identify DNA associated with that specific cancer.
The goal is to determine whether evidence of cancer remains in the body and whether changes in ctDNA levels may provide insight into treatment response or the risk of recurrence.
While the concept is exciting, experts caution that the science is still evolving.
Why Are Doctors Using It Differently?
One of the most common frustrations patients express is hearing that one physician recommends Signatera while another does not.
According to Dr. Nasrazadani, this variation is largely because there are currently no standardized guidelines directing physicians on exactly how to use the information these tests provide.
Although Signatera is commercially available and may be covered by insurance, organizations such as the National Comprehensive Cancer Network (NCCN) have not yet established clear recommendations regarding how the results should influence treatment decisions.
As a result, physicians often rely on their own clinical judgment and experience when deciding whether to order the test and how to interpret the findings.
This does not mean one physician is right and another is wrong. Rather, it reflects the reality that the medical community is still learning how best to incorporate this emerging technology into patient care.
The Challenge of Interpreting Results
For many patients, the most difficult aspect of Signatera is understanding what the results actually mean.
Researchers generally agree that a negative result is preferable to a positive one. Beyond that, however, many important questions remain unanswered.
For example:
- What level of circulating tumor DNA is clinically significant?
- Does a low positive result carry the same meaning as a high positive result?
- Do results behave differently in triple-negative, hormone receptor-positive, HER2-positive, or inflammatory breast cancer?
- Should treatment be changed based on a positive result alone?
At this time, the answers are not always clear.
Some patients experience fluctuating results that move between positive and negative. Others may have a positive ctDNA result while imaging scans remain clear. Conversely, some patients may have visible disease on imaging while ctDNA remains undetectable.
These situations highlight why Signatera is currently viewed as one piece of information rather than a standalone decision-making tool.
Why the Test Can Cause Anxiety
The uncertainty surrounding ctDNA testing can create significant emotional stress.
Patients living with IBC understand better than most how important it is to remain vigilant. Many have experienced delayed diagnoses or misdiagnoses and are understandably eager for any information that may provide insight into their disease.
During the discussion, the physicians shared the perspective of a metastatic breast cancer patient who explained that she wanted access to the information, even if it created anxiety.
Her reasoning was simple: she believed patients should have the right to decide whether they want that information.
At the same time, both physicians emphasized the importance of understanding the limitations of the test. While Signatera can provide data, data does not always provide definitive answers.
Why Timing Matters
Another important factor is when the test is performed.
Patients receiving chemotherapy, radiation, surgery, or other treatments intended to eliminate microscopic disease may still have detectable ctDNA.
That does not necessarily mean treatment is failing.
In fact, these therapies are specifically designed to target cancer cells that may remain after diagnosis. Researchers are still working to understand how ctDNA levels should be interpreted during active treatment and in the months following therapy.
This is one reason many physicians are cautious about making major treatment changes based solely on a Signatera result.
The Importance of Research
Throughout the discussion, both physicians emphasized that ctDNA testing represents an active area of research.
Clinical trials and observational studies are underway to better understand how these tests can be used in patients with inflammatory breast cancer and other breast cancer subtypes.
Researchers are exploring questions such as:
- Can ctDNA predict treatment response?
- Can it identify recurrence earlier than imaging?
- Can it help determine which therapies are most effective?
- Can it identify patients who may benefit from more aggressive or less aggressive treatment?
Answering these questions requires large numbers of patients, carefully designed studies, and years of follow-up.
While progress is being made, experts caution that the field has not yet reached the point where ctDNA testing alone can reliably guide treatment decisions.
Reasons for Hope
Although many questions remain unanswered, there is considerable reason for optimism.
Just a few years ago, the ability to detect and measure circulating tumor DNA in this way did not exist. Today, researchers are collecting data, conducting studies, and gaining new insights into how cancer behaves at the molecular level.
For patients living with IBC, these advances represent meaningful progress.
Every study contributes to a growing body of knowledge that may eventually help physicians identify recurrence sooner, personalize treatment more effectively, and improve outcomes for future patients.
As Dr. Nasrazadani noted during the discussion, these technologies have opened the door to asking questions that were not previously possible. While the answers are still emerging, the potential impact is significant.
The Bottom Line
For now, Signatera should be viewed as a promising tool rather than a definitive answer.
A positive result does not automatically mean recurrence is imminent. A negative result does not guarantee cancer will never return. Most importantly, results should always be interpreted within the context of a patient’s overall clinical picture.
Patients considering ctDNA testing should have open conversations with their healthcare team about the benefits, limitations, and implications of the information it provides.
The science is advancing rapidly, and researchers remain hopeful that tests like Signatera will play an increasingly important role in breast cancer care.
Until then, experts encourage patients to stay informed, ask questions, and remember that one test result is only one piece of a much larger picture.