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Research uncovers how breast cancer cells “hibernate” to avoid treatment
Researchers have identified a key mechanism used by cancer cells to evade therapy by remaining in a dormant state
Scientists have discovered how breast cancer cells can “hibernate” to avoid treatment and “wake up” years later, causing a relapse that is more difficult to treat.
The research, published in the journal Cancer Discovery, has revealed the role of “epigenetics” in controlling how cancer cells can become dormant and suggested a strategy to target it before the cells “wake up”.
Epigenetic changes alter how your body reads your DNA, without changing the DNA code itself.
Patients with oestrogen receptor positive (ER+) breast cancer – which make up 80 per cent of all breast cancers – have a continued risk of their cancer recurring for many years or even decades after their original diagnosis and surgery. To reduce their risk of relapse, patients undergo five to ten years of hormone therapy to target any remaining cancer cells.
The team at The Institute of Cancer Research, London, found that this hormone therapy could, in some cases, play a role in triggering epigenetic changes that alter the state of some breast cancer cells, causing them to become dormant and evade treatment.
The researchers discovered that specific changes in key epigenetic regulators that control gene transcription, including the modification of histone H3 at lysine 9 (H3K9me2), were responsible for this dormant state. These changes remain until the cell “wakes up” and begins dividing rapidly again.
The scientists found that blocking these regulators – by inhibiting the enzymes that catalyse them – prevented the cells from becoming dormant, and killed the cancer cells that were already dormant. They also discovered that in people with low expression of these enzymes, their cancer had a lower risk of coming back years later.
The team studied ER+ breast cancer cells that they tagged with unique barcodes, an innovative way to study millions of cells through space and time. They mimicked hormone therapy treatment on the cells and saw that while most cells died, others became dormant and stopped proliferating.
Using mass spectrometry, the researchers discovered that hormone therapy treatment triggered changes to histone modifications, including H3K9me2, as the cells went into dormancy.
Histone modifications are chemical tags that are added to or removed from DNA, or the proteins DNA is wrapped around. Epigenetic modifications such as this are chemical changes to the three-dimensional structure of DNA, which do not alter the DNA code itself but can control access to genes.
The researchers set out to uncover whether blocking these epigenetic changes could prevent the cells from becoming dormant and evading treatment. To do this, they inhibited the enzyme G9a, which catalyses H3K9me2.
The researchers first tested this on cells which had just been treated with hormone therapy and found that it prevented the cancer cells from entering dormancy – in fact, it killed the cells.
Then, they tested it on cells which were already in a dormant state and found that inhibiting G9a killed dormant cancer cells.
To understand the importance of G9a in people, the researchers studied a cohort of patients with ER+ breast cancer. They found that for those who had low expression of enzymes such as G9a, their breast cancer had a significantly lower risk of relapse over the course of 15 to 20 years.
Professor Luca Magnani, professor of epigenetic plasticity at The Institute of Cancer Research, said: “After surgery to remove primary oestrogen receptor positive breast cancer, patients are given five to ten years of hormone therapy which aims to kill any remaining cancer cells.
“We know that this doesn’t work for all patients though, as their breast cancer can return years, or even decades later. We wanted to better understand why breast cancer does return so we can hopefully find ways to stop it – so people don’t have to live in fear or face the devastating news of a relapse.
“Our research identified a key mechanism used by cancer cells to evade therapy by remaining in a dormant state, hibernating before they ‘wake up’ years later and begin to rapidly divide again.
“I hope our early findings will next lead to research to target these dormant breast cancer cells so that one day, without the need for years of hormone therapy, patients can be sure that their cancer will not return.”
Professor Kristian Helin, chief executive of The Institute of Cancer Research, and a leading researcher of epigenetics and cancer, said the research adds to the growing body of evidence for the role of epigenetic regulation in cancer’s complex behaviour.
“We know that cancer will adapt and evolve to evade treatment, and this study shows how it will lie dormant to hide from treatment,” she said.
“Drugs targeting epigenetic modifications are already in development, and I hope that this research will pave the way to new treatments that prevent breast cancer from returning.”
Dr Tayyaba Jiwani, science engagement manager at Cancer Research UK, added: “Breast cancer survival has doubled in the UK over the last 50 years thanks to better detection and screening, but there are still more than 11,000 deaths from this type of cancer every year.
“Our research has made it increasingly clear that cancer cells can lie dormant in the body for many years before being triggered to reawaken, causing cancer to return. This study uses an innovative approach to analyse the genetics of these dormant cells and gain important insight into the mechanisms leading to dormancy.
“Although at an early stage, the findings reveal potential new targets for the development of innovative treatments that prevent breast cancer from coming back.”
Xella Health has integrated Oura wearable data into its women’s health platform, allowing members to share trends with clinicians alongside diagnostic results.
Members can choose to share information including sleep, heart rate variability, resting heart rate, temperature trends, recovery, activity and menstrual-cycle data.
The integration is intended to help clinicians investigate biological factors that may explain changes in members’ wearable data and symptoms.
Kelly Lacob, chief executive and co-founder of Xella Health, said: “Wearables detect that something in the body has changed, but wearable data alone can’t tell a woman why or what to do next with that information.”
“By pairing continuous physiological monitoring from Oura with Xella’s multiomic diagnostics and physician-guided care, we enable women to understand how specific health concerns are impacting her biometrics, and vice versa how her daily habits are impacting her overall health and specific conditions or life stages she is navigating.
“Further, we are able to track how her relevant vitals and biometrics respond to specific interventions or treatment plans, so we can optimise her care more efficiently.
“Ultimately, this partnership helps us better address her symptoms today whilst also proactively optimising her long-term health trajectory for decades to come.”
Xella Health combines AI, multiomic testing and physician-guided telehealth care through a membership platform.
Multiomic testing analyses several types of biological information.
Xella said its testing assesses hormonal and metabolic health, inflammation, nutritional status, reproductive health and cardiometabolic risk.
Physicians use those findings to develop personalised care plans that may include clinical treatments.
Clinicians can then review shared Oura trends alongside diagnostic results and member check-ins to monitor progress and adjust care over time.
The company said providers interpret biometric data in the context of each member’s health conditions, goals and treatment plan.
The integration focuses on fertility, perimenopause, hormonal and cardiometabolic health, as well as women’s longer-term health.
Oura has expanded its women’s health offerings through integrations connecting wearable measurements with other sources of health data.
In February, it partnered with at-home hormone tracking company Mira, allowing users to view hormone test results alongside sleep, temperature and readiness data in the Mira app.
The integration is intended to help users track patterns related to fertility, menstrual cycles and perimenopause.
That month, Oura also introduced a women’s health AI model for testing through Oura Labs.
Integrated into Oura Advisor, the model combines biometric data with clinician-reviewed medical information to provide guidance on menstrual cycles, pregnancy and menopause.
In May, the company launched menopause insights and hormonal birth control support.
Its Menopause Insights offering uses a questionnaire covering 22 symptoms of menopause alongside wearable data, while birth control support helps users understand their biometric trends in the context of hormonal contraception.
Partners of women going through menopause will be invited to experience hot flushes using a menopause simulator at a support event in Hull next month.
Health group Over The Bloody Moon will bring one of its MenoVests to the Menopaus’ull Support Network event, allowing people to experience a hot flush.
Sarah Weichardt, who co-manages the project, said: “We’re particularly interested in getting men along to come and experience the MenoVest, just so that they can understand what women go through.
“It’s not just a hot flush, it’s what the hot flush brings with it.
“So it could be panic, it could be anxiety. It’s experiencing it all at the same time.”
MenoVest is billed as the ‘world’s first’ wearable menopause simulator – a garment worn over regular clothing that generates realistic, intense hot flush sensations while the wearer carries on with everyday work tasks.
After just a few minutes wearing it, people gain a genuine sense of what these symptoms feel like, building empathy and highlighting why better support matters during this transition.
Weichardt said she hoped the vest would give people a “better understanding of what women are going through”.
“The more people we can get to experience it, the better,” she added.
Short-term oral HRT was linked to a 60 per cent higher rate of serious blood clots in women aged 50 to 69, a large study found.
The increased rate was seen among women using oral hormone replacement therapy for less than a year as well as those treated for more than five years.
By contrast, transdermal HRT, delivered through skin patches, gels or sprays, was not associated with the same increased clot risk.
Researchers at North Zealand Hospital in Denmark analysed health registry data from more than one million Danish women aged 50 to 69 between 2003 and 2021.
During the study period, 9,807 women experienced venous thromboembolism, a serious blood clot in a vein. A further 18,460 had a stroke and 11,974 had a heart attack.
Each affected woman was matched by age with five women who had not experienced the same condition. Researchers adjusted the analysis for other factors, including medical history, that could influence risk.
They then examined HRT prescriptions, including the dose and duration of treatment, and looked for associations with blood clots, stroke and heart attack.
Overall, oral HRT was associated with a 60 per cent higher rate of venous thromboembolism, with increased rates seen for both oestrogen-only therapy and treatment combining oestrogen with progestogen.
Venous thromboembolism occurs when a blood clot forms in a vein. A clot in a deep vein can break away and travel to the lungs, causing a potentially fatal pulmonary embolism.
Women taking oral HRT for less than a year had the same raised blood clot risk as those using it for more than five years.
Even a daily oral dose below 1mg was found to significantly increase blood clot risk.
Women taking a daily oral dose above 1mg for more than five years had an 80 per cent higher risk of both heart attack and stroke.
For women taking a high oral dose for more than one year, the study found a 40 per cent higher risk of heart attack and a 50 per cent higher risk of stroke.
The researchers highlighted the importance of choosing the type, dose and duration of treatment carefully, particularly for patients vulnerable to blood clots.
Dr Robert Storey, professor of cardiology at the University of Sheffield, who was not involved in the research, said the findings demonstrated the importance of ensuring cardiovascular risk factors were “well controlled” in women taking oral HRT.
He added: “The study emphasises the superior safety of patches over oral treatment.”
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