A powerful new drug for advanced breast cancer can be used to treat emerging tumours, months before they have a chance to grow, helping to keep patients well for longer and delaying the need for later-line therapies including chemotherapy.
Results of a global study, funded by AstraZeneca and co-led by researchers at The Institute of Cancer Research, London, The Royal Marsden NHS Foundation Trust and Institut Curie, Paris, were presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago on 1 June 2025.
The results found that patients with advanced hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer who were given the new drug, called camizestrant, in combination with a CDK4/6 inhibitor cut the chances of their cancer getting worse by over half (56 per cent), allowing them to stay on first-line therapy for longer.
Using liquid biopsies to guide treatment
The SERENA-6 phase III trial is also the first global trial to demonstrate that using circulating tumour DNA (ctDNA) blood tests to guide treatment at the right time — before clinical signs of progression appear — has a significant clinical benefit for this group of patients.
Findings from the trial were simultaneously published in The New England Journal of Medicine.
Experts now hope the findings have the potential to become a new treatment strategy for patients with this common type of advanced breast cancer.
Around 55,000 women are diagnosed with breast cancer in the UK every year and 11,500 will die from the disease. Around 70 per cent of patients have HR+, HER2- breast cancer.
Understanding ESR1 mutations
Some patients go on to develop mutations in a gene called ESR1 gene, which programmes the oestrogen receptor, allowing the cancer to grow and resist hormone-blocking treatments. Although ESR1 mutations are rare at diagnosis of advanced breast cancer, they emerge during first-line therapy in around 40 per cent of patients.
First-line therapy for HR+, HER2‑ advanced breast cancer is usually a cyclin-dependent kinase (CDK) 4 and 6 inhibitor drug plus an aromatase inhibitor (a type of hormone treatment). If this treatment fails, chemotherapy can be an option but delaying this is highly important for patients because of the toxic side effects it brings.
Camizestrant, which was discovered and developed by AstraZeneca, is a type of drug described as a ‘next-generation’ oral selective estrogen receptor degrader (SERD). It works by blocking and breaking down oestrogen receptors in breast cancer cells. Camizestrant was designed to target the ESR1 mutations tested for in the ctDNA blood tests. Camizestrant not only prevents oestrogen from attaching to cancer cells but also destroys the receptors themselves, making it harder for the cancer to resist treatment.
The SERENA-6 study tested whether switching to camizestrant from an aromatase inhibitor, whilst continuing treatment with the same CDK 4/6 inhibitor to treat tumours with emerging ESR1 mutations could extend the benefit of first line treatment and delay the need for later-line therapies.
Breakthrough results
To be eligible to take part in the study, 3,325 patients with HR+, HER2 negative advanced breast cancer (who had been on first-line treatment for at least six months) from 23 countries were screened for ESR1 mutations using ctDNA testing every 8-12 weeks. Of that number, 548 patients tested positive for ESR1 mutations during the screening period, and 315 were randomised onto the study.
Half of the patients were given camizestrant, alongside their CDK4/6 inhibitor plus a dummy pill instead of their aromatase inhibitor. Patients on the control arm continued with their aromatase inhibitor and CDK4/6 inhibitor plus a dummy pill instead of camizestrant.
The results showed that the camizestrant combination reduced the risk of breast cancer progression or death by over half (56 per cent), based on the reported hazard ratio of 0.44. The median progression free survival time for patients taking the camizestrant combination was 16 months, compared with 9.2 months for patients on the control arm.
The camizestrant combination was well tolerated, with only a few patients (1 per cent) experiencing side effects that led them to discontinue the treatment. The results also showed that the therapy regime reduced the risk of a deterioration in patients’ general health and quality of life by 47 per cent (based on the reported hazard ratio of 0.53), compared with the control group, demonstrating the benefit of patients remaining on first-line therapy.
A decade of research
The Breast Cancer Clinical Trials Team that co-led the SERENA-6 trial are based in the Ralph Lauren Research Wing, Kuok Research Centre within the Oak Cancer Centre, which was funded by The Royal Marsden Cancer Charity.
Scientists working in the Breast Cancer Now Toby Robins Research Centre at the ICR and The Ralph Lauren Centre for Breast Cancer Research at The Royal Marsden, funded by The Royal Marsden Cancer Charity, and The National Institute for Health and Care Research Royal Marsden Biomedical Research Centre, have been leading pioneering research into the use of liquid biopsies to detect breast cancer relapse and guide treatment for more than a decade.
Co-principal investigator Professor Nick Turner, Professor of Molecular Oncology at The Institute of Cancer Research, London, and Director of Clinical Research and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:
“This is a pivotal moment in breast cancer care. These results demonstrate that using liquid biopsy blood tests to spot emerging resistance in tumours, before they start to grow and make the patient unwell, can guide early intervention with camizestrant to delay disease progression in patients with ESR1 mutations.
“This proactive approach not only extends the benefit of first line therapy but also redefines how we think about drug resistance in this type of breast cancer.
This is a potential new treatment strategy in oncology to treat developing resistance before it causes disease progression.
“Ongoing trials are also examining the use of camizestrant in broader first-line populations from the start of their treatment, as well as in the early breast cancer setting, to determine how best to integrate camizestrant into long-term treatment strategies to benefit breast cancer patients.”
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:
“The results of the SERENA-6 trial represent more than a clinical milestone – they represent a transformational shift in how we approach precision medicine.
"The Institute of Cancer Research has played a major role in advancing ctDNA testing for breast cancer, particularly in early detection and relapse prediction – so it is very exciting to see this technology being used to delay disease progression in patients and extend the benefits of first-line treatment in patients with this type of advanced breast cancer and delay the need for chemotherapy for as long as possible.
“These breakthroughs are helping shape personalised breast cancer treatment, allowing doctors to adjust therapies earlier and improve patient outcomes.”
Professor Nicholas van As, Chief Medical Officer at The Royal Marsden NHS Foundation Trust, said:
“Innovative ctDNA trials at The Royal Marsden have transformed the way clinicians tailor cancer treatments and detect relapse in patients before clinical signs of progression appear.
“It is hugely exciting that the SERENA-6 trial has evolved this thinking and clinicians can use it to personalise kinder treatments regimes for this group of patients and improve their outcome.”