In a significant leap forward for cancer research, scientists have discovered a groundbreaking method to detect and destroy dormant breast cancer cells—those elusive remnants that often evade treatment and trigger relapse years later.
This breakthrough offers new hope for long-term remission and could revolutionise how breast cancer is treated, shifting the focus from survival to complete eradication. Experts say the findings may pave the way for therapies that not only treat the disease but prevent its return entirely.
Scientists at the University of Pennsylvania have shown for the first time that it’s possible to detect dormant cancer cells in breast cancer survivors and eliminate them with repurposed drugs, potentially preventing recurrence.
In a clinical trial, existing medications cleared these hidden cells in most participants, leading to survival rates above 90%. The findings open a new era of proactive treatment against breast cancer’s lingering threat, offering hope to survivors haunted by the fear of relapse.
A first-of-its-kind, federally funded clinical trial has shown it’s possible to identify breast cancer survivors who are at higher risk of their cancer coming back due to the presence of dormant cancer cells and to treat these cells with repurposed, existing drugs effectively.
The research, led by scientists from the Abramson Cancer Centre of the University of Pennsylvania and Penn’s Perelman School of Medicine, was published today in Nature Medicine.
While breast cancer survival continues to improve, thanks to advances in detection and treatment, when breast cancer relapses — or returns after initial treatment — it is still incurable.
For the 30 per cent of women and men who do relapse, the only option is continuous and indefinite treatment, which cannot eliminate the cancer. Some breast cancers, like triple-negative and HER2+, recur within a few years, and others, like ER+, can recur decades later.
Until now, there has not been a way to identify those breast cancer survivors who harbour the dormant cells that lead to recurrence in real time and to intervene with a treatment that can prevent incurable relapse.
In a randomised phase II clinical trial with 51 breast cancer survivors, existing drugs were able to clear dormant tumour cells from 80 per cent of the study participants.
The three-year survival rate without any disease recurrence was above 90 per cent in patients who received one drug and 100 per cent for patients who received both study drugs.
“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 tumour cells is a strategy that holds real promise, and I hope it ignites more research in this area.”
The study builds on previous research that showed how dormant tumour cells continue to lie 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, they 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.
Lewis Chodosh, MD, PhD, chair of Cancer Biology and senior author of the study, previously led research to identify the pathways that allow dormant tumour cells to survive in patients for decades.
“Our research shows that this sleeper phase represents an opportunity to intervene and eradicate the dormant tumour 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 tumour 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 more prolonged survival without cancer recurrence. The drugs target autophagy and mTOR signalling, which the researchers found were key mechanisms to allow the tumour cells to remain dormant.
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 tumour cells in participants’ bone marrow.
If dormant tumour cells were found, patients were then eligible to enrol in the Phase II CLEVER clinical trial, which randomised patients to receive six cycles of either monotherapy with one of two study drugs or combination therapy with both drugs.
The treatment cleared dormant tumour cells in most patients after six to 12 months. After a median follow-up time of 42 months, only two patients in the study have experienced a cancer recurrence.
“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 centres across the country.
Patients interested in learning more about these or other breast cancer clinical trials at Penn Medicine should contact BreastCancerClinicalTrials@pennmedicine.upenn.edu.
The research was made possible with funding from the National Cancer Institute (R01CA208273) and Department of Defence (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.