MRD stands for minimal residual disease, the tiny number of cancer cells that can remain in the body after treatment and that may not show up on routine scans. Detecting MRD is like finding a few seeds left in a garden after clearing: it helps doctors predict the chance of relapse and measure how effective a therapy is, which investors watch because MRD results can influence clinical trial success, regulatory decisions, and a drug’s market potential.
adjuvantmedical
An adjuvant is an ingredient added to a vaccine or other therapy to strengthen or shape the body’s response to the main active component, like a helper that makes the primary ingredient work better or longer. For investors, adjuvants matter because they can change how well a product performs, alter dosing and safety profiles, affect regulatory review, and therefore influence clinical success, market size and competitive advantage.
cdk4/6 inhibitormedical
A CDK4/6 inhibitor is a type of cancer drug that blocks two proteins (CDK4 and CDK6) that tell cells to divide, effectively slowing or stopping the growth of tumors. Think of it as cutting power to a photocopier that keeps making cancer cells; that control can shrink tumors or delay progression. For investors, these drugs matter because clinical trial results, regulatory approvals, patent life, safety issues and competition directly affect sales potential and company value.
hr+/her2-medical
A cancer subtype where tumor cells have hormone receptors for estrogen and/or progesterone (HR+) but lack excess HER2 protein (HER2−). Think of receptors as locks: HR+ tumors have locks that can be targeted by hormone-blocking drugs, while HER2− means a different lock is absent, so HER2-targeted medicines won’t work. For investors this classification matters because it determines which therapies are appropriate, how large the patient market is, and which clinical trials and regulatory paths are relevant.
endocrine therapymedical
Endocrine therapy is a medical treatment that reduces or blocks hormones that help certain tumors grow, for example by lowering production of the hormone or preventing it from attaching to cancer cells. Think of it as cutting off the fuel supply to slow or stop growth. Investors care because these therapies drive sales, long-term treatment demand, regulatory milestones and clinical trial outcomes that directly affect healthcare companies’ revenues and valuations.
distant recurrence-free intervalmedical
Distant recurrence-free interval is the length of time after initial cancer treatment during which the disease does not come back in a different part of the body (metastasis). For investors, it’s a key measure of a therapy’s ability to delay or prevent serious relapse—longer intervals suggest stronger clinical benefit, which can improve a drug’s regulatory prospects, adoption by doctors, and commercial value. Think of it like the warranty period before a major problem reappears.
overall survivalmedical
Overall survival is the average or median length of time patients remain alive after starting a treatment or entering a clinical study, measured regardless of cause of death. Investors care because it is a clear, hard measure of a therapy’s real-world benefit — like timing how long a new battery actually runs — and strong improvements in overall survival can drive regulatory approval, market adoption and revenue potential.
single-armmedical
A single-arm study is a clinical trial that gives all participants the same treatment and does not include a separate comparison group or placebo. Think of it like testing a new recipe by serving it to diners without offering a control dish — you can see how people respond, but you can’t directly compare results to another option. For investors, single-arm trials can speed development and reduce cost but leave more uncertainty about how a treatment stacks up against existing therapies and how regulators will view the evidence.
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Signatera™ will be used to identify patients who may be able to delay or defer adjuvant CDK4/6 inhibitor therapy in intermediate-risk HR+/HER2- breast cancer
SIGNAL is a new group of Natera-sponsored interventional trials designed to establish the clinical utility of MRD-guided treatment de-escalation strategies across multiple cancer types
AUSTIN, Texas--(BUSINESS WIRE)--
Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, today announced enrollment of the first patients in SIgnatera-Guided iNterventionAL (SIGNAL)-ER 101, a prospective, single-arm, multi-center study evaluating Signatera MRD-guided de-escalation in early-stage breast cancer.
The current standard of care recommends two or three years of an adjuvant CDK4/6 inhibitor in combination with endocrine therapy for patients with intermediate-risk, hormone receptor (HR) positive, HER2 negative, early stage breast cancer. This is despite the fact that only ~3% of eligible patients derive benefit, over 60% of patients experience serious adverse events,1-2 and the U.S. retail costs can be over $400,000 for a full course of treatment. Meanwhile, data presented at SABCS 2025 from the PALLAS trial show that HR+ breast cancer patients who tested MRD-negative with Signatera had excellent long-term outcomes, with >95% distant recurrence-free interval at 5 years. This suggests that MRD-negative patients can safely defer CDK4/6 inhibition with no impact to clinical outcomes, with the provision that it be added if and when MRD is detected on serial testing using a TOMR (Treatment on MRD) approach.
SIGNAL-ER 101 plans to enroll approximately 725 patients across 50 sites in the United States. Patients who test MRD-positive will receive endocrine therapy plus CDK4/6 inhibitors, while those who test MRD-negative (the vast majority of patients) will receive endocrine therapy alone with quarterly Signatera monitoring. Patients who become MRD-positive during surveillance will be eligible to initiate CDK4/6 inhibition at that time, consistent with the TOMR approach.
“Many women with this type and stage of breast cancer are overtreated, which can have a profound impact on their quality of life,” said Minetta Liu, M.D., chief medical officer, oncology and early cancer detection at Natera. “SIGNAL-ER 101 is a key part of our evidence generation roadmap, to support Signatera-guided treatment optimization without compromising the survival benefit from CDK4/6 inhibitors. This approach also allows patients to get the most effective treatment when Signatera shows it is necessary.”
SIGNAL-ER 101 is the first in a series of innovative Natera-sponsored SIGNAL trials across multiple cancer types, designed to demonstrate that MRD-negative patients may be able to delay or defer treatment. There are many instances of overtreatment in cancer. This concept has already been studied in the IMvigor011 trial where MRD-negative patients with muscle-invasive bladder cancer achieved 97% overall survival at 2 years without any adjuvant therapy, and in the GALAXY and CALGB/SWOG 80702 trials, where MRD-negative patients with colorectal cancer saw no clinical benefit from adjuvant chemotherapy and celecoxib, respectively.
References
Johnston SRD, Toi M, O’Shaughnessy J, et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. The Lancet Oncology. 2023;24(1):77-90. doi:10.1016/S1470-2045(22)00694-5.
Slamon DJ, Lipatov O, Nowecki Z, et al. Ribociclib plus endocrine therapy in early breast cancer. New England Journal of Medicine. 2024;390(12):1080-1091. doi:10.1056/NEJMoa2305488.
About Natera
Natera™ is a global leader in cell-free DNA and precision medicine, dedicated to oncology, women’s health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard-of-care to protect health and inform earlier, more targeted interventions that help lead to longer, healthier lives. Natera’s tests are supported by more than 400 peer-reviewed publications that demonstrate excellent performance. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California, and through Foresight Diagnostics, its subsidiary, operates an ISO 27001-certified and CAP-accredited laboratory certified under CLIA in Boulder, Colorado. For more information, visit www.natera.com.
Forward-Looking Statements
All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera’s plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera’s expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to our efforts to develop and commercialize new product offerings, whether the results of clinical or other studies will support the use of our product offerings, the impact of results of such studies, our expectations of the reliability, accuracy, and performance of our tests, or of the benefits of our tests and product offerings to patients, providers, and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera’s recent filings on Forms 10-K and 10-Q, and in other filings Natera makes with the SEC from time to time. These documents are available at www.natera.com/investors and www.sec.gov.
