After treatment for cancer, the waiting can be the hardest part: months between scans, wondering whether the cancer is truly gone. Signatera is a blood test that tries to answer that question earlier, by looking for tiny fragments of DNA released by cancer cells. It can sometimes detect cancer coming back many months before anything shows on a scan. That is powerful information, and it also raises a question medicine has not fully answered yet: if the blood test is positive but the scans are clear, what should be done? This guide explains how Signatera works, what positive and negative results mean, what the evidence does and does not show, and why clinical trials are one of the main options for people with a positive result.
Signatera positive, but your scans are clear?
Some clinical trials are designed for exactly this situation, testing whether early treatment can prevent a visible recurrence.
What Signatera looks for
When cancer cells die, they release small pieces of their DNA into the bloodstream, known as circulating tumor DNA, or ctDNA. Signatera, made by Natera, is a tumor informed test: it first sequences the DNA from a sample of your own tumor, usually from surgery or biopsy, and then builds a personalized blood test that looks for the specific mutations found in your cancer. Because it is tailored to your tumor, it can detect extremely small amounts of ctDNA. Doctors use it to look for minimal residual disease, meaning cancer cells left behind after treatment that are too few to see on a scan. It is used in several cancers, most often colorectal cancer and breast cancer.
How early it can detect recurrence
In a study of people with early stage breast cancer tested every six months after treatment, Signatera detected ctDNA before the recurrence was found by standard methods in 30 of the 34 people whose cancer returned, with a median lead time of 10.5 months and in some cases more than three years. Other studies have reported similar lead times. A negative result is reassuring: people whose test stays negative have a low risk of recurrence in the following months. In the US, Medicare covers Signatera for monitoring recurrence in breast cancer.
What a negative result means
A negative result means no tumor DNA was found in that blood sample. It is good news and is linked to a lower risk of recurrence, but it is not a guarantee, because a very small amount of cancer may release too little DNA to detect. That is why testing is usually repeated over time, and why it does not replace recommended treatment such as hormone therapy, or follow up for new symptoms.
What a positive result means
A positive result means tumor DNA was found, and in breast cancer studies, most people with a confirmed positive result went on to have a recurrence. Typically, a positive result leads to scans to look for visible cancer. Sometimes they show a recurrence, and treatment follows the usual path for that. Often, though, the scans are clear. This is the situation called molecular relapse: the blood says the cancer is likely returning, but there is nothing yet to see or treat. It is a difficult place to be, and it is where the evidence is still being built.
What the evidence does not yet show
It is not yet proven that starting treatment early, based on a positive blood test alone, helps people live longer. For that reason, major oncology groups have not yet endorsed routine ctDNA monitoring for everyone after breast cancer treatment, and decisions are made case by case with your oncologist. The question of what to do with a positive result is exactly what a growing number of clinical trials are designed to answer.
Why trials enroll people with a positive result
Because molecular relapse is a new situation, research has moved quickly to study it. Current trials enroll people whose ctDNA turns positive after treatment to test whether adding or switching treatment can clear the tumor DNA and prevent visible recurrence, while other studies use ctDNA to decide who needs more or less treatment from the start. In the US, dozens of breast cancer studies currently recruiting involve ctDNA testing, some specifically for people with a positive result and no visible disease. For someone with a positive test and clear scans, a trial can offer a structured plan and close monitoring at the moment when standard care has the least to offer.
How to find a study
AllClinicalTrials.com lists breast cancer and other cancer studies recruiting across the US and Canada, including studies that use ctDNA testing; see our breast cancer clinical trials page, or the page for your cancer type. The application takes about 5 minutes: you answer questions about your diagnosis, treatments, and test results, including Signatera, and if a study near you looks like a match, the research team contacts you. Nothing is decided until you have gone through informed consent, and participation is voluntary at every step.
Three things to have ready: your Signatera results and their dates, your cancer type and stage at diagnosis, and the treatments you have completed.
Common questions
What does a positive Signatera test mean? That tumor DNA was found in your blood, which signals a high risk that the cancer is returning. It usually leads to scans; if they are clear, you and your oncologist discuss options, which can include a clinical trial.
How accurate is Signatera? In breast cancer studies it detected recurrence ahead of standard methods in most people whose cancer returned, with a median lead time of about 10 months. A negative result is linked to a low short term risk but is not a guarantee.
How far in advance can Signatera detect recurrence? In one breast cancer study, the median lead time was 10.5 months, and in some cases more than three years before recurrence was found by standard methods.
Is Signatera covered by insurance? Medicare covers it for monitoring recurrence in breast cancer, and coverage by other insurers varies. Your oncologist's office can check.
Should everyone get Signatera after breast cancer? Not necessarily. Major guidelines have not yet endorsed routine monitoring for everyone because it is not proven that acting early improves survival. It is a decision to make with your oncologist.
What happens if my Signatera is positive but scans are clear? There is no single standard approach yet. Options include closer monitoring, repeat testing, adjusting treatment, or joining a clinical trial designed for this situation.
Is Signatera only for breast cancer? No. It is used in several cancers, most often colorectal and breast cancer, and trials using ctDNA are underway in many cancer types.
Do cancer trial participants get paid? Some studies offer compensation for time and travel, and study related care is typically provided at no cost to participants. Compensation varies by trial and is always described during the informed consent process before you agree to anything.
See breast cancer clinical trials recruiting now
Browse open studies, filter by location, and apply in about 5 minutes: Breast Cancer Clinical Trials.