News
New approach to treating aggressive breast cancers shows significant improvement in survival
A new treatment approach significantly improves survival rates for patients with aggressive, inherited breast cancers, according to Cambridge researchers.
In a trial where cancers were treated with chemotherapy followed by a targeted cancer drug before surgery, 100 per cent of patients survived the critical three-year period post-surgery.
The discovery could become the most effective treatment to date for patients with early-stage breast cancer with inherited BRCA1 and BRCA2 gene mutations.
Breast cancers with faulty copies of the BRCA1 and BRCA2 genes are challenging to treat, and came to public attention when actress Angelina Jolie, a BRCA1 carrier, underwent a preventative double mastectomy in 2013.
Current standard treatment aims to shrink the tumour using chemotherapy and immunotherapy, before removing it through surgery. The first three years after surgery is a critical period, when there is the greatest risk of relapse or death.
The Partner trial took a different approach and demonstrates two innovations: the addition of olaparib and chemotherapy pre-surgery, and the benefits of careful timing of when the treatments are given to patients. Taken as tablets, olaparib is a targeted cancer drug already available on the NHS.
Led by Addenbrooke’s Hospital, part of Cambridge University Hospitals (CUH) NHS Foundation Trust and the University of Cambridge, the trial saw patients recruited from 23 NHS sites across the UK.
Results show that leaving a 48-hour “gap” between chemotherapy and olaparib, leads to better outcomes, possibly because a patient’s bone marrow has time to recover from chemotherapy, while leaving the tumour cells susceptible to the targeted drug.
Of the 39 patients who received chemotherapy followed by olaparib, only one patient relapsed three years after surgery and 100 per cent of patients survived.
In comparison, the survival rate for the control arm was 88 per cent three years after surgery. Of the 45 patients on the control arm who received chemotherapy only, nine patients relapsed, of whom six died.
Jackie Van Bochoven, 59, from South Cambridgeshire, was diagnosed in February 2019 with a small but aggressive tumour.
Van Bochoven said: “When I had the diagnosis, I was completely shocked and numb, I thought about my children, and my mum and sister who were diagnosed with breast cancer. I was pretty worried.
“Six years on, I’m well and cancer free. I’m back at work, enjoying life and spending time with my family. When you’ve had cancer, I think you look at life differently and every day is a bonus.”
The findings have the potential to be applied to other cancers caused by faulty copies of BRCA genes, such as some ovarian, prostate and pancreatic cancers.
It may also have cost-saving benefits for the NHS, as patients currently offered olaparib take the drug post-surgery for 12 months, whereas patients on the trial took the tablets pre-surgery for 12 weeks.
Addenbrooke’s consultant and trial lead, Professor Jean Abraham said: “It is rare to have a 100 per cent survival rate in a study like this and for these aggressive types of cancer. We’re incredibly excited about the potential of this new approach, as it’s crucial that we find a way to treat and hopefully cure patients who are diagnosed with BRCA1 and BRCA2 related cancers.”
Professor Abraham, who is also Professor of Precision Breast Cancer Medicine at the University of Cambridge, said trialling the 48-hour gap approach followed a “chance conversation” with Mark O’Connor, chief scientist in Early Oncology R&D at nearby AstraZeneca.
Mark O’Connor said: “The Partner trial highlights the importance of detecting and treating cancer early, and the value of innovative science in informing clinical trial design, in this case using bone marrow stem cells to identify the combination gap schedule.
“While the findings need to be validated in a larger study, they’re incredibly exciting, and have the potential to transform outcomes for patient populations who have unmet clinical need.”
This type of collaboration between NHS, academia and industry reflects the vision of Cambridge Cancer Research Hospital, a specialist cancer research hospital due to be built on Europe’s leading life sciences campus, the Cambridge Biomedical Campus.
It will bring clinical expertise from Addenbrooke’s Hospital with world-class scientists from the University of Cambridge, Cancer Research UK Cambridge Centre, and industry partners together in one location to create new diagnostics and treatments to detect the earliest signs of cancer and deliver personalised, precision medicine.
Chief executive of Cancer Research UK, Michelle Mitchell, said: “One of the best ways that we can beat cancer sooner is by making more effective use of treatments that are already available to us.
“While this research is still in its infancy, it is an exciting discovery that adding olaparib at a carefully-timed stage of treatment can potentially give patients with this specific type of breast cancer more time with their loved ones.
“Research like this can help find safer and kinder ways to treat certain types of cancer. Further studies in more patients are needed to confirm whether this new technique is safe and effective enough to be used by the NHS.”
Professor Abraham and team are now planning the next phase of the research, which will look to replicate the results in a larger study and confirm that the Partner approach offers a less toxic treatment for patients as well as being more cost effective, compared to the current standard of care.
Simultaneous exposure to toxic chemicals and climate-related heat may be worsening fertility harms across humans and wildlife, research suggests.
The review of scientific literature looks at how endocrine-disrupting chemicals, often found in plastic, together with climate-related effects such as heat stress, are each linked to lower fertility and fecundity, meaning the ability to reproduce, across species including humans, wildlife and invertebrates.
Though the reproductive harms of each issue in isolation are well studied, there is little research on what happens when living organisms are exposed to both.
“Together, the two issues are likely to pose a greater threat to fertility, and the additive effect is “alarming”, said Susanne Brander, a study lead author and courtesy faculty at Oregon State University.
“You’re not just getting exposed to one, but two, stressors at the same time that both may affect your fertility, and in turn the overall impact is going to be a bit worse,” Brander said.
The paper looked at 177 studies.
Shanna Swan, a co-author on the new paper, co-produced a 2017 study that found sperm levels among men in western countries had fallen by more than 50 per cent over four decades. Other research has suggested human fertility has been declining at a similar rate.
The University of Washington’s Institute for Health Metrics and Evaluation has previously said the world was approaching a “low-fertility future”, with more than three quarters of countries below replacement rate by 2050.
The new paper’s authors focused on the effects of endocrine-disrupting chemicals and substances, including microplastics, bisphenol, phthalates and PFAS.
These are thought to cause a range of serious reproductive problems, disrupt hormones and be a potential driver of falling fertility.
Brander said the harms linked to these chemicals are often similar across organisms, from invertebrates to humans.
Phthalates, for example, have been linked to altered sperm shape in invertebrates, spermatogenesis in rodents, meaning sperm production, and reduced sperm counts in humans.
PFAS are also thought to affect sperm quality, and both have been linked to hormone disruption.
The chemicals are widespread in consumer goods, so people are often regularly exposed.
Meanwhile, previous research has shown how rising temperatures, lower oxygen levels and heat stress, among other effects linked to climate change, may also worsen infertility.
Heat stress has been found to affect human hormones, and is linked to spermatogenesis in rodents and bulls.
Research shows temperature also plays a role in sex determination in fish, reptiles and amphibians.
The species has evolved to choose which sex it produces in part based on temperature, and the heating planet can “push it too far in one direction or the other, which overrides that evolutionary benefit”, Brander said.
Similarly, many endocrine disruptors may alter environmental sex determination.
The study set out some of the overlapping effects of chemical exposure and climate change across taxonomic groups, from invertebrates to humans.
In birds, for example, exposure to increased temperature, PFAS, organochlorines and pyrethroids may each individually cause abnormal sperm, increased fledgling mortality, abnormal testes and population decline.
“What happens if they’re exposed to more than one of those stressors at the same time? There has been little exploration of that question.
“Even if there have not been a lot of studies looking at these simultaneously, if you have two different factors that both cause the same adverse effect, then there’s a likelihood that they are going to be additive,” Brander said.
Katie Pelch, a senior scientist with the Natural Resources Defense Council nonprofit, who was not part of the study, said the authors had reviewed high-quality science.
She said she wanted to see more examples of the overlap in impacts, but agreed with the overall premise.
“It is likely [multiple stressors] would have an additive effect, at very least, even if they have different mechanisms of harm,” Pelch added.
The solution to the systemic problems would involve tackling climate change and reducing the use of toxic chemicals.
The study cites the global reduction in the use of DDT and PCBs achieved under the Stockholm Convention as an example of an effective measure, but Brander said much more is needed.
“There is enough evidence in both areas to act to reduce our impact on the planet,” she said.
Home blood pressure checks after hypertensive pregnancy could cut the risk of heart attack, stroke and potentially early death, research suggests.
Women who regularly monitored their blood pressure in the weeks after giving birth, and had doctors tailor their medication if needed, had better functioning arteries nine months later than those who received routine care.
When the medication was adjusted to account for blood pressure changes, the women ended up with less stiff arteries, an effect researchers estimated could reduce the future risk of heart attack or stroke by 10 per cent.
Paul Leeson, professor of cardiovascular medicine who led the study, said the findings suggested that the weeks after birth provided a “powerful and often overlooked opportunity” to protect women’s future health.
“By simply monitoring blood pressure at home, new mothers with hypertensive pregnancies can protect their bodies from future damage,” he said.
High blood pressure, in the form of gestational hypertension or pre-eclampsia, where there are signs of organ damage, affects 5 to 10 per cent of pregnant women.
The condition can damage the mother’s organs and endanger the baby’s life.
Beyond the immediate threat to mother and baby, hypertension in pregnancy can raise the risk of long-term problems, with women three times more likely to develop high blood pressure and twice as likely to have heart disease later in life.
The Oxford team recruited 220 women who developed hypertension in pregnancy. All were on blood pressure medication but were due to reduce their dosage and eventually stop taking the drugs.
In the study, 108 women had standard care in which their medication was reduced based on a few blood pressure checks in the eight weeks after giving birth.
The remaining 112 women used a monitor to check their blood pressure at home each day.
They entered the readings into an app shared with doctors who, if needed, changed their medication day to day, with the aim of giving them better control of their blood pressure.
The new approach led to much better control of the women’s blood pressure, and in tests six to nine months later the women had less stiff arteries.
Stiff arteries are less effective at expanding and contracting, which can drive high blood pressure and ultimately the formation of clots that can block blood vessels and cause heart attacks and strokes.
Trials are now under way to find effective ways of rolling out blood pressure monitoring to women after hypertensive pregnancies. One option is for specialist NHS clinics to deliver the care.
Dr Sonya Babu-Narayan, clinical director at the British Heart Foundation, which funded the work, said the results highlighted a crucial window after birth when paying close attention to blood pressure could help protect women’s heart health for years to come.
“We now look forward to seeing results from larger studies with longer follow-up to see how this might save women’s lives,” she said.
Weight loss jabs are being studied to see if they could help women with polycystic ovary syndrome (PCOS)
The condition, which affects up to one in ten women, changes how the ovaries work and is linked to infertility and weight gain.
Dr Shagaf Bakour has won a £60,000 NHS research grant through Sandwell and West Birmingham NHS Trust to look at whether drugs such as Mounjaro and Ozempic might help.
“The research could lead to earlier support, better long-term health, and more joined-up care for a condition that affects many women but is still often overlooked,” she said.
Women with PCOS have higher levels of male hormones and can suffer from irregular periods and symptoms such as excess body or facial hair, the NHS said.
Associated weight gain can also lead to an increased risk of diabetes and heart problems.
Bakour, a gynaecologist and director of medical education at Aston Medical School, will work with a team to evaluate the effect of the weight loss medicines on metabolic and reproductive outcomes.
The drugs mimic a hormone called GLP-1, which suppresses appetite.
Bakour, alongside Dr Hoda Harb, a consultant obstetrician and gynaecologist at the NHS trust, will review existing evidence on their use and assess how they help patients with PCOS.
“The aim is to give women with PCOS evidence-informed, clearer treatment options and more consistent care,” she said.
“The project hopes to show whether these medicines can improve both general health and fertility health, while also helping local services develop clearer care pathways.
Prof Elizabeth Hughes, director of research and development at the NHS trust, said the effects of PCOS, including infertility, were “very emotive subjects”.
“We should be doing all we can within research and development to advance healthcare for women and to better help future generations with this condition,” she added.
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