For women with HER2 positive early-stage breast cancer taking Herceptin for six months could be as effective as 12 months in preventing relapse and death, and can reduce side effects, finds new research.

The PERSEPHONE trial, a £2.6 million study funded by the NIHR with translational research funded by Cancer Research UK, recruited over 4,000 women and compared a six month course of treatment of Herceptin with the current standard of 12 months for women with HER2-positive early-stage breast cancer. This is the largest trial of its kind examining the impact of shortening the duration of Herceptin treatment.

Herceptin, has been a major breakthrough, prolonging and saving the lives of women with breast cancers that carry the HER2 receptor on the surface of their cancer cells. Around 15 out of every 100 women with early breast cancers have HER2 positive disease. Herceptin is a targeted therapy that works by attaching to the HER2 receptors preventing the cancer cells from growing and dividing. It has rapidly become standard of care and based on clinical research a 12 month treatment course was adopted. However, a further clinical study suggested a shorter duration could be as effective, significantly reducing side effects and cost both to patients and to the NHS.

The trial, led by a team from the University of Cambridge and Warwick Clinical Trials, the University of Warwick, found that 89.4% of patients taking six months treatment were free of disease after four years compared with 89.8% of patients taking treatment for 12 months. These results show that taking Herceptin for six months is as effective as 12 months for many women. In addition, only 4% of women in the six month arm stopped taking the drug early because of heart problems, compared with 8% in the 12 month arm. Women also received chemotherapy (anthracycline-based, taxane-based or a combination of both) while enrolled in the trial.

Lead study author Professor Helena Earl, Professor of Clinical Cancer Medicine, University of Cambridge, Cancer Research UK Cambridge Centre and Cambridge BRC researcher, said “The PERSEPHONE trials team, patient advocates who have worked with us on the study and our investigators are very excited by these results. We are confident that this will mark the first steps towards a reduction of Herceptin treatment to six months in many women with HER2-positive breast cancer. However, any proposed reduction in effective cancer treatment will always be complex and very challenging, and women currently taking the medication should not change their treatment without seeking advice from their doctor. There is more research to be done to define as precisely as possible the particular patients who could safely reduce their treatment duration. We are poised to do important translational research analysing blood and tissue samples collected within the trial to look for biomarkers to identify subgroups of different risk where shorter/longer durations might be tailored.”

Professor Hywel Williams, Director of the NIHR Health Technology Assessment Programme that funded the PERSEPHONE study said: “This is a hugely important clinical trial that shows that more is not always better. Women will now have the potential to avoid unnecessary side effects of longer treatment without losing any benefit. In turn, this should help save vital funds for the NHS and prompt more studies in other situations where the optimum duration of treatment is not known. It is unlikely that research like this would ever be done by industry, so I am delighted that the NIHR are able to fund valuable research that has a direct impact on patients.”

Professor Charles Swanton, Cancer Research UK’s chief clinician, said: “This is a critically important study that the breast cancer field has been eagerly awaiting. Targeted therapies, while effective, come at a huge health economic cost to the NHS as well as potentially causing side effects such as heart problems. Despite years of research, we haven’t been able to establish the optimal duration of Herceptin treatment, either to delay cancer coming back or to cure patients with early HER2+ breast cancer following surgery.

“The exciting early key findings from this study show that 6 months of Herceptin might be as effective as 12 months, and it may also be safer and with fewer side effects. By analysing tumour and blood samples, the researchers will now try to understand which patients can stop Herceptin at 6 months and which patients need extended therapy.”

Maggie Wilcox, President of Independent Cancer patients Voice (ICPV) who is the patient lead for the PERSEPHONE trial, said “I am delighted to have been part of this landmark trial which is an important step to reduce the length of treatment whilst not changing effectiveness. Most trials add novel treatments to standard practice whilst this has set out to reduce duration of Herceptin. The collection of the patient reported experiences throughout the trial will greatly inform future practice and benefit patients. ICPV is working with the Persephone team to help disseminate these exciting results’.

The results of the trial, PERSEPHONE, will be presented at the upcoming 2018 ASCO Annual Meeting in Chicago. The full report, which will include analysis to determine the impact of treatment length on quality of life and a detailed cost effectiveness analysis, will publish in the NIHR journals library. Visit the project page for more information.

Have you thought about signing up to the NIHR BioResource as a healthy volunteer?

As far as clinical research is concerned, it could be one of the best things you ever do!

When volunteers take part in our studies, they help researchers to understand more about the role of specific genes involved in the development of disease. And that could help them to identify better treatments or cures for disease.

So what happens when you join the BioResource as a healthy volunteer?

You can find out more elsewhere on the BioResource website – and you could also watch below a short film of one of their healthy volunteers, Michael, as he talks openly about what was involved for him when he signed up.

Scientists say they have identified genes that cause a deadly heart condition – pulmonary arterial hypertension (PAH) – that can only be cured by transplants of the heart or lungs.

Pulmonary Arterial Hypertension (PAH) is a fatal lung disease and causes the walls of the arteries become thick and stiff, narrowing the space for blood to pass through and increasing blood pressure then leading to heart failure.

The disease kills 50% of those affected within five years, but little was known about what caused the condition in some people. Now experts say they have discovered five genes that cause the illness and could pave the way for more treatments.

Scientists carried out the largest ever genetic study of the disease by analysing the genomes – the unique sequence of a person’s DNA – of more than 1,000 PAH patients for whom the cause of the illness was unknown.

They found that mutations in five genes were responsible for causing the illness in these people, including in four genes that were not previously known to be involved in the disease. In people with the condition these genes fail to effectively produce the proteins that are required for the structure, function and regulation of the body’s tissues, researchers found.

Nick Morell, the lead author of the paper and professor at the NIHR Cambridge BRC and British Heart Foundation, said: “Identifying the nature of these new genes and mutations in the new genes tells you what causes the disease.

“It allows you to design and come up with potential new ways of treating the disease because you have really well-grounded knowledge about what’s actually causing it in cases where you find these mutations,” he explained.

More information about this research can be found in Nature Communications

The NIHR Cambridge Biomedical Research Centre, NIHR BioResource, BHF Cambridge Centre of Cardiovascular Research Excellence, the UK Medical Research Council supported this study

Four of Cambridge University’s leading female clinical researchers want to inspire more women to go for the profession’s top jobs.

Christi Deaton, Fiona Karet, Rebecca Fitzgerald and Sadaf Farooqi all hold Professorships at the University of Cambridge School of Clinical Medicine and the NIHR Cambridge Biomedical Research Centre (BRC), based on the Cambridge Biomedical Campus.

The number of women in top clinical academic posts at the School rose from 13% to more than 17% over 2012-17 – and they want that figure to increase even more by reaching out to young female medics and other health care professionals as well as school and college students.

Speaking ahead of International Women’s Day on 8 March, they outlined to the NIHR Cambridge BRC how women can succeed in a male-dominated profession.

Florence Nightingale Foundation Chair of Clinical Nursing Research Prof Christi Deaton, from USA, said: “We want to encourage nurses, midwives and allied health professionals [still largely female professions], who may have had little or no exposure to research training in their undergraduate courses, to develop research skills and address questions of importance to patients and their practices.

“We help them with training and link them with senior researchers who can take on a mentoring role.”

Prof Deaton benefited early on in her career from having a role model who mentored and encouraged her – at a time when nurses were not expected to be researchers or scientists. She said: “In the US children learn about Sacagawea, a Native American woman who guided explorers Lewis and Clark across the wilderness to the Pacific Coast.

“My colleagues and I called our mentor [Professor Sandra Dunbar] Sacagawea because she always led the way!”

Professor Fiona Karet is a renal medicine researcher and also the School’s Director of Organisational Affairs. She led the School to achieving and renewing an Athena SWAN Silver award – which recognises advancement of gender equality – and part of her remit is to even the playing field for women in research, especially in mid-career.

Prof Karet said: “Outreach is an important part of all our roles. We talk to young female medics about the possibilities open to them and we visit schools and colleges to talk about our work and inspire future researchers.

“Senior male engagement is critical to changing the landscape for aspiring women clinical academics and we have worked hard on this, and also to provide confidence building and other training opportunities for women at this stage when many drop out.”

This is appreciated by women at all stages of their academic career, including Professor Rebecca Fitzgerald, part of the research team that developed the ‘pill on a string’ which can detect oesophageal cancer at an early stage.

She said: “My research team includes talented women with the potential to succeed in clinical academic posts, and it’s important for them to have good support around them, so that they have the confidence and self-belief to progress in their careers.

“Our role as senior clinical academics is to remove the barriers stopping women from applying for these senior posts and show the way.”

Obesity researcher Professor Sadaf Farooqi said: “At any early stage in my career, the top clinical jobs were mostly held by men– there were very few female role models.

“That situation is changing. Here in Cambridge, people like Rebecca are making ground-breaking discoveries in diseases that kill many people. There will be girls who will read this article and see Rebecca Fitzgerald and I hope they will think that may be one day they might be able to do that.”

The photo above shows from l-r: Professors Rebecca Fitzgerald, Sadaf Farooqi, Christi Deaton, Fiona Karet.