News
Study identifies why some breast cancers become resistant to hormone therapy
Scientists analysed genetic mutations in the circulating tumour DNA of patients with advanced ER-positive breast cancer
A team of British researchers have discovered why some advanced oestrogen receptor (ER) positive breast cancers become resistant to hormone therapy.
Researchers at The Institute of Cancer Research, London, found that for four per cent of patients with breast cancer, mutations in the oestrogen receptor gene (ESR1), called F404, when combined with specific pre-existing mutations, caused resistance to fulvestrant hormone therapy.
They found that cells with these mutations remained sensitive to a range of compounds which are currently being tested in clinical trials.
The scientists hope that in the future, if these new drugs are approved, patients likely to develop treatment resistance through F404 mutations could be identified with a blood test and offered new, alternative treatments.
Fulvestrant is a widely used type of hormone therapy that is usually given to people with ER-positive breast cancer, either as a first line of treatment or once other drugs have stopped working. However, patients’ cancers will very often develop resistance to the treatment over time.
‘This could revolutionise the way we treat breast cancer’
The research, which was published in the journal Cancer Discovery, involved studying blood samples donated by people taking part in the plasmaMATCH clinical trial.
In the trial, researchers used liquid biopsies to analyse small traces of cancer DNA in the blood which have been released from tumour cells.
The team analysed these blood samples, looking at genetic mutations in the circulating tumour DNA of patients with advanced ER-positive breast cancer and observing how they responded to fulvestrant.
ER-positive breast cancers use oestrogen in the body to help them to grow, and hormone therapies like fulvestrant target the oestrogen receptor to prevent this.
Researchers in this study wanted to understand how mutations in the gene that codes for the oestrogen receptor, ESR1, can contribute to fulvestrant resistance.
They found that in four per cent of patients, following fulvestrant treatment, their breast cancer developed specific mutations in the ESR1 gene, called F404.
These new mutations only occurred in patients who already had certain existing mutations in the ESR1 gene before treatment. The researchers noted that the combined effect of these pre-existing and new mutations was a “profound resistance” to fulvestrant.
The team then tested a series of hormone therapies currently in clinical development on cancer cells with the F404 mutations. They were encouraged to discover that fulvestrant-resistant cancer cells with F404 mutations were sensitive to all four therapies tested.
Professor Nicholas Turner, professor of molecular oncology at The Institute of Cancer Research and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, said: “Our study makes use of innovative blood tests which detect genetic changes present in a patient’s cancer, without the need for any invasive procedures.
“The discovery of these specific genetic changes in oestrogen receptor positive breast cancer helps to explain one mechanism by which some patients develop resistance to fulvestrant, and which upcoming treatments will be likely to work instead.
“This could revolutionise the way we treat breast cancer, by making use of these simple blood tests to match patients to alternative treatments, bringing them the best possible outcome.”
Dr Kotryna Temcinaite, head of research communication and engagement at Breast Cancer Now, said: “These findings help us understand how secondary breast cancer can become resistant to hormone therapies like fulvestrant and what other treatments we could use in the future if this resistance happens.
“With an estimated 61,000 people living with secondary breast cancer in the UK, research like this is vital”.
Dr Nisha Duggan, science engagement manager at Cancer Research UK, added: “Research discoveries like this help scientists find better ways to treat cancer.
“Understanding why a drug like fulvestrant stops being effective will help researchers and doctors identify the best medicines available for people living with certain types of breast cancer and develop new therapies.”
She added: “This would provide people living with specific types of cancer with more effective treatment options, ultimately helping them to live longer, better lives.”
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An early PET scan after one cycle of chemotherapy may help predict how aggressive breast cancer responds to treatment, a study suggests.
Research led by The Institute of Cancer Research, London and King’s College London suggests that an early scan taken after one cycle of chemotherapy could help predict how well a patient’s cancer will respond to treatment.
The study focused on patients with triple-negative breast cancer (TNBC), an aggressive form of the disease in which cancer cells lack receptors for the hormones oestrogen and progesterone, as well as the HER2 protein.
Patients with TNBC are usually treated with chemotherapy prior to surgery. While many respond well, residual disease at surgery, typically around six months later, is associated with a significantly poorer prognosis. Identifying people sooner who are unlikely to respond remains a major clinical challenge.
The research explored whether using PET imaging shortly after treatment begins, rather than relying only on MRI scans later in the treatment process, could provide earlier insight into how a patient’s cancer is responding. Twenty-two patients were recruited, with fourteen undergoing FDG-PET scans before treatment and after the first cycle of chemotherapy.
The findings, published in Clinical Cancer Research, showed that changes seen on PET scans after just one cycle of chemotherapy were strongly associated with subsequent response, including whether there was no detectable cancer, known as a complete response, by the end of treatment. Importantly, early PET response showed stronger associations with treatment outcomes than standard mid-treatment MRI scans in this study.
Being able to identify patients who are not responding well at an early stage could allow clinicians to adjust treatment sooner or consider alternative approaches. These findings may also support future strategies to better tailor treatment intensity to individual patients.
The study also compared two types of PET tracers, FDG and FLT, to determine which was most suitable. While both met the study’s technical criteria, FDG-PET was selected for further evaluation due to its better image quality, greater consistency and wider use in clinical practice.
The research also explored how imaging changes after just one cycle of chemotherapy relate to the body’s immune response to treatment. Biopsies taken before and after the first cycle of chemotherapy showed that an increase in immune cells within the tumour was strongly associated with both early PET changes and improved treatment outcomes.
The researchers emphasise that these findings now need to be validated in larger studies. Future work will aim to confirm these results in broader patient groups and explore more accessible imaging approaches, such as ultrasound, alongside PET and MRI.
Sheeba Irshad, professor of cancer immunology at King’s College London and lead of the Breast Cancer Now KCL Research Unit, said:
“In patients who had PET scans both before treatment and after the first cycle, we found that this early scan could predict whether they were likely to achieve a complete response by the end of treatment. These findings highlight the potential of early imaging to guide treatment decisions, and now need to be validated in larger, modern clinical trials.”
Andrew Tutt, professor of breast oncology at The Institute of Cancer Research, London, said:
“Research that helps us determine early who is already benefitting from standard neoadjuvant chemotherapy and who might benefit from clinical trials to find better treatments is vital. This study shows that FDG-PET may have great value in this regard. We hope to be able to design studies that further investigate and validate these findings.”
The study was supported by funding from King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, Breast Cancer Now, Cancer Research UK, and Guy’s and St Thomas’ Charity.
We are excited unveil the three finalists competing for one of the Femtech World Awards’ most coveted honours: the Startup of the Year Award, sponsored by Future Fertility.
This award celebrates an early-stage company making a bold impact in women’s health through innovation, vision and execution.
The winner will be announced at our virtual ceremony on 19 June, with the decision made by a representative from category sponsor Future Fertility.
Congratulations to the shortlist and thank you to everyone who entered or nominated.
Startup of the Year Shortlist
Hello Inside is the first women’s health AI company to turn daily metabolic signals into outcomes women feel and healthcare systems reimburse.
Women’s health has long been under-researched, and current AI benchmarks fail on women’s health questions roughly sixty percent of the time.
Hello Inside built the architecture to close that gap.
Across four years and 12,000+ validated metabolic profiles, three in four women improve at least one symptom within ninety days.
They lose four kilograms in three months, moving from overweight into the healthy range. In a clinical study with Alisa Vitti’s Flo Living, 91.9 per cent reduced PMS burden within sixty days.
U-Ploid is an early-stage biotechnology company tackling one of the most fundamental challenges in fertility care: the sharp, age-related decline in egg quality that limits outcomes across IVF and egg freezing.
While much of the field focuses on improving assessment and selection, U-Ploid is developing a first-in-class therapeutic approach designed to improve egg quality itself by addressing the biological causes of age-related chromosomal errors.
Supported by strong preclinical evidence and now advancing into human studies, U-Ploid combines scientific rigour, regulatory discipline and long-term vision to help redefine what is possible in fertility care.
Gestational diabetes is a strong risk factor for future type 2 diabetes, even in women with normal pre-pregnancy weight, according to a study at the University of Gothenburg.
The researchers call for earlier testing and better follow-up.
“Our results show that gestational diabetes functions as a kind of stress test for the body’s ability to manage blood sugar, and identifies women with a greatly increased risk of future type 2 diabetes”, said Jon Edqvist, PhD and affiliated to research at the University of Gothenburg, and operating room nurse at Sahlgrenska University Hospital.
Gestational diabetes is a special type of diabetes that can affect pregnant women.
The condition is defined as elevated blood sugar levels, without previously known diabetes. Treatment involves self-monitoring of blood sugar, advice on lifestyle habits and, if necessary, medication.
Identifying gestational diabetes is important because the disease increases the risk of complications such as preeclampsia, the need for a cesarean section and high birth weight for the baby.
Those who have had gestational diabetes are also at higher risk of later developing type 2 diabetes.
In the current study, published in eClinicalMedicine, researchers now show that gestational diabetes is a strong indicator of future risk of developing type 2 diabetes, even in women with normal weight before pregnancy.
Elevated risk even with normal weight
The study is based on data from the Medical Birth Registry on just over 1.15 million first-time mothers in Sweden, who gave birth between 1987 and 2019. 16,870 women with confirmed gestational diabetes were compared with age-matched women without the diagnosis. The median follow-up period was nine years.
The results show that women with a BMI of 35 and above, i.e. severe obesity, had an almost tenfold increased risk of developing gestational diabetes compared to women with normal weight.
The risk of subsequent type 2 diabetes also increased with higher BMI, but it was significantly increased even with normal weight, which the researchers describe as particularly worrying.
More follow-up and more studies
The researchers behind the study welcome the recently updated recommendations on gestational diabetes in Sweden, where a higher proportion of pregnant women at increased risk are expected to be offered testing earlier in pregnancy, and if necessary, interventions.
“Diagnostics and care of gestational diabetes have looked very different in different parts of the country,” said Annika Rosengren, professor at the University of Gothenburg.
“There is a need for both improved follow-up after gestational diabetes, and more studies that investigate how such follow-up affects future health and prognosis”
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