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Researchers have discovered that dormant breast cancer cells can be detected and wiped out with existing drugs, dramatically lowering the risk of relapse. The breakthrough brings new hope to survivors haunted by the fear of recurrence.

Breakthrough Trial Targets Dormant Breast Cancer Cells

A landmark federally funded clinical trial has provided the first real evidence that doctors can pinpoint breast cancer survivors at higher risk of relapse by detecting dormant cancer cells, and that these hidden cells can be successfully treated using already available drugs. The work, led by researchers at the Abramson Cancer Center of the University of Pennsylvania and Penn’s Perelman School of Medicine, appears in the journal Nature Medicine.

Although survival rates for breast cancer continue to improve thanks to better screening and therapies, the disease remains incurable once it comes back after initial treatment. About 30 percent of women and men experience a relapse, leaving them dependent on ongoing treatment that cannot completely remove the cancer. Some forms, such as triple negative and HER2+, often reappear within a few years, while ER+ cases can resurface even decades later. Until now, doctors had no way to identify which survivors carried dormant cells that fuel recurrence or to step in with a therapy that could prevent it.

The Hidden Threat of Cancer Relapse

In the randomized phase II trial, 51 breast cancer survivors were tested with existing drugs, which successfully cleared dormant tumor cells in 80 percent of participants. After three years, the survival rate without any return of disease exceeded 90 percent among patients given a single drug and reached 100 percent for those who received both medications.

“The lingering fear of cancer returning is something that hangs over many breast cancer survivors after they celebrate the end of treatment,” said principal investigator Angela DeMichele, MD, MSCE, FASCO, the Mariann T. and Robert J. MacDonald Professor in Breast Cancer Research. “Right now, we just don’t know when or if someone’s cancer will come back—that’s the problem we set out to solve. Our study shows that preventing recurrence by monitoring and targeting dormant tumor cells is a strategy that holds real promise, and I hope it ignites more research in this area.”

Survivors’ Hope: Preventing Recurrence Before It Starts

The study builds on previous research that showed how dormant tumor cells continue to lay in wait in some patients after breast cancer treatment. These so-called “sleeper cells,” also referred to as minimal residual disease (MRD), can reactivate years or even decades later. Because they are not “active” cancer cells and can be scattered throughout the body, they do not show up on standard imaging tests that are used to watch for breast cancer recurrence.

Once the sleeper cells begin to expand and circulate in the bloodstream, it can lead to the spread of metastatic breast cancer. Patients who have MRD are more likely to experience breast cancer recurrence and have decreased overall survival.

Why Dormant Cells Escape Detection

Lewis Chodosh, MD, PhD, chair of Cancer Biology and senior author of the study, previously led research to identify the pathways that allow dormant tumor cells to survive in patients for decades.

“Our research shows that this sleeper phase represents an opportunity to intervene and eradicate the dormant tumor cells before they have the chance to come back as aggressive, metastatic disease,” Chodosh said. “Surprisingly, we’ve found that certain drugs that don’t work against actively growing cancers can be very effective against these sleeper cells. This tells us that the biology of dormant tumor cells is very different from active cancer cells.”

In the preclinical part of the latest research publication, Chodosh’s team conducted a series of experiments in mice to better understand the underlying mechanisms. They showed that two different drugs—approved by the FDA to treat other conditions—could effectively clear MRD in mice, resulting in longer survival without cancer recurrence. The drugs target autophagy and mTOR signaling, which the researchers found were key mechanisms to allow the tumor cells to remain dormant.

How FDA-Approved Drugs Target Dormant Cells

DeMichele’s team first enrolled breast cancer survivors who had completed treatment within the last five years and had clear scans into a screening study that looked for dormant tumor cells in participant’s bone marrow.

If dormant tumor cells were found, patients were then eligible to enroll in the Phase II CLEVER clinical trial, which randomized patients to receive six cycles of either monotherapy with one of two study drugs, or combination therapy with both drugs. The treatment cleared dormant tumor cells in most patients after six to 12 months. After a median follow-up time of 42 months, only two patients on the study have experienced a cancer recurrence.

The CLEVER Trial: Promising Early Results

“We want to be able to give patients a better option than ‘wait and see’ after they complete breast cancer treatment,” DeMichele said. “We’re encouraged by these results that we’re on the right track.”

The team is already enrolling patients in two larger, ongoing studies to confirm and extend the results of the CLEVER study: the Phase II ABBY clinical trial and the Phase II PALAVY clinical trial, available at several cancer centers across the country. Patients interested in learning more about these or other breast cancer clinical trials at Penn Medicine should contact [email protected].

Reference: “Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial” by Angela DeMichele, Amy S. Clark, Emily Shea, Lauren J. Bayne, Christopher J. Sterner, Killian Rohn, Samantha Dwyer, Tien-chi Pan, Isoris Nivar, Yan Chen, Paul Wileyto, Lindsay R. Berry, Shannon Deluca, Jessica Savage, Igor Makhlin, Dhruv K. Pant, Heather Martin, Adetutu Egunsola, Nathan Mears, Brooke L. Goodspeed, Elizabeth M. Chislock, Jewell Graves, Jianping Wang, Natalie Shih, George K. Belka, Don Berry, Anupma Nayak, Michael Feldman and Lewis A. Chodosh, 2 September 2025, Nature Medicine.
DOI: 10.1038/s41591-025-03877-3

The research was made possible with funding from the National Cancer Institute (R01CA208273) and Department of Defense (BC160784), with additional support from the V Foundation, Breast Cancer Research Foundation, QVC “Shoes on Sale,” Avon Foundation, Raynier Institute & Foundation, and generous philanthropic donations. DeMichele previously reported interim outcomes data from the study at the European Society for Medical Oncology (ESMO) Congress 2023.

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Researchers tracking over 11,000 adults reveal that simply walking longer each day, rather than faster, may help protect against one of the world’s leading causes of disability.

Study: Volume and Intensity of Walking and Risk of Chronic Low Back Pain. Image credit: Chay_Tee/Shutterstock.com

Millions of people worldwide suffer from chronic low back pain, but regular physical activity could reduce it. A recent study in JAMA Network Open examines the potential benefit of daily walking volume and intensity in lowering the risk of chronic low back pain.

Introduction

Chronic low back pain is the most common type of chronic pain and the leading cause of functional disability, as well as the single largest contributor to years lived with disability. With the number of cases only set to increase, it is essential to identify modifiable risk factors and frame suitable preventive interventions and policies.

Physical activity is key to managing chronic low back pain, but the type and amount remain unclear. Recent evidence suggests that walking reduces the risk of recurrence in nonspecific chronic low back pain. The current study examined whether walking is associated with a lower risk of chronic low back pain, but it cannot prove causality as an observational study.

About the study

The current prospective study was based on a group of 11,194 participants at least 20 years old, who were part of the Norwegian Trøndelag Health (HUNT) Study. About 60% were women.

Baseline measurements were obtained between 2017 and 2019, with follow-up assessments in 2021-2023. All participants were free of chronic low back pain at baseline. Chronic low back pain was defined as pain that had lasted for three or more months during the last 12 months.

The walking parameters used in this study were daily walking volume in minutes per day and walking intensity measured as metabolic equivalent of task (MET) per minute. Accelerometers were used to collect this data.

Study findings

At the beginning of the study, the participants wore accelerometers for an average of 5.7 days, with a mean walking volume of ~104 minutes/day. During the follow-up period (4.2 years on average), about 15% developed one or more episodes of chronic low back pain.

Walking volume

Those who walked more had a lower risk of chronic low back pain. On average, walking for more than 100 minutes/day was linked to a 23% lower risk of chronic low back pain, compared with <78 minutes of walking per day. Those who walked 78-100 minutes/day also had a 13% lower risk.  

The effect was stronger and more consistent among older adults (65 years or above) than among younger people, but both men and women showed comparable benefits. 

Walking intensity

Again, higher-intensity walking was associated with a lower risk of chronic low back pain. Compared to the reference intensity of <3 MET per minute, a higher intensity of 3-3.1 MET/minute was linked to a 15% lower risk of low back pain.

The risk dropped by 16% and 18% at walking intensities of 3.12-3.26 MET/minute and 3.27 MET/minute or higher, respectively. However, these associations were weaker once walking volume was considered.

The reduction in low back pain risk increased with increased walking volume until about 100 minutes/day, with a more gradual increase thereafter. Similarly, walking intensity was linked to a reduced back pain risk until about 3.2 MET/minute, though this was much weaker when adjusted for walking volume.

When both were considered together, there was no apparent benefit with increased walking intensity among those who walked more than 125 minutes daily. Below this, those who walked more intensely had a greater reduction in low back pain risk.

Conclusion

“These findings indicate that policies and public health strategies promoting walking may help to reduce the burden of chronic low back pain.”

The authors emphasized that daily walking volume appeared more important than walking intensity. Still, they cautioned that the study design does not establish cause and effect and that residual confounding is possible. They also noted limitations such as reliance on a single baseline measurement and potential recall bias in pain reporting.

With its ease, universal availability, and numerous benefits, walking could be widely encouraged as a preventive measure for chronic low back pain, pending confirmation in future studies.

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(Barcelona, Spain September 9, 2025, 10:15 a.m. CEST / UTC +2) — A new study presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer (WCLC) demonstrates that monitoring circulating tumor DNA (ctDNA) can refine and personalize the use of consolidation immunotherapy in patients with limited-stage small cell lung cancer (LS-SCLC).

The research, led by scientists at the National Cancer Center of China, assessed ctDNA in 177 patients with LS-SCLC treated with chemoradiotherapy (CCRT), 77 of whom received consolidation immune checkpoint inhibitors (ICIs). Circulating tumor DNA was measured at multiple time points to evaluate its ability to predict survival outcomes and immunotherapy benefits.

“This is the first study to show that early ctDNA detection after induction chemotherapy can help identify patients who are more likely to benefit from consolidation immunotherapy,” said Dr. Nan Bi, from the Chinese Academy of Medical Sciences. “It’s a step toward precision immunotherapy in limited-stage SCLC.”

Key Findings:

• Consolidation ICI improved overall survival vs. CCRT alone (HR: 0.41; p = 0.031).
• Patients who were ctDNA-positive at post-induction had significantly better PFS and OS with ICI compared to CCRT alone.
• ctDNA-negative patients did not show added benefit from ICI.
• Maintaining ctDNA negativity during immunotherapy was associated with better prognosis.
• ctDNA at post-induction (t1) was more predictive of treatment response than ctDNA post-radiotherapy (t2).

The study used next-generation sequencing (NGS) with a 139-gene lung cancer panel to assess ctDNA at ultra-deep coverage (30,000×). Advanced statistical models including time-dependent Cox regression were employed to eliminate immortal time bias.

“These findings offer a compelling rationale for integrating ctDNA-based stratification in future LS-SCLC trials and may help guide real-time decisions on the use of consolidation ICIs,” Dr. Bi said.

About the IASLC: