Being diagnosed with breast cancer is devastating news, and for women with the most aggressive form there used to be just a 50 per cent chance of surviving.
But in 2002 that all changed.
Research nurses recruited thousands of patients into an international clinical trial, to find out whether a new drug could help those patients live longer.
The study was called the HERA trial, the drug was Herceptin and the results were astonishing.
As the NHS marks 70 years, we reflect on the significance of the HERA trial and look at how it paved the way for Herceptin’s use in a range of cancers, offering hope to patients all around the world.
Being part of the trial
The HERA trial was aimed at helping a very specific group of breast cancer patients, who have cancers producing an abnormal quantity of a protein known as HER2. That HER2, on the surface of their cancerous cells was key to those cells dividing uncontrollably to grow into tumours.
Siân Whelan is the Cancer Research UK senior research nurse at Singleton Hospital in Swansea. She remembers the trial starting.
“As it happens my very first day working here was the site initiation visit for the HERA trial. The drug company running the study, Roche, came to check that everything was in place.”
At that time, HER2 screening wasn’t routine so patients were asked to consent for their tissue samples to be sent over to a central testing facility in Germany.
“It’s something we take for granted now,” said Siân, “but in the early stages testing wasn’t happening routinely. We did know though that if patients were HER2-positive then their disease was much more aggressive – but there was no treatment.”
HERA aimed to change this, testing the drug Herceptin that targeted the HER2 receptor protein, sticking to it and blocking its effects. It was a global study, with Singleton and Velindre hospitals being Wales’ sites for the trial, which saw patients receive Herceptin after their surgery and chemotherapy. Some patients also had radiotherapy depending on the type of breast surgery they required.
The trial had three ‘arms’ or possible treatments: patients either received the current gold standard treatment of surgery plus chemotherapy, and possibly radiotherapy; Herceptin for one year post-treatment; or they received Herceptin for two years. It was a randomised controlled trial, to avoid accidental bias or ‘placebo’ effects, so patients were randomly allocated to the treatment ‘arms’.
“We spoke to patients about this,” explained Siân, “and of course it meant extending their treatment time, but those patients were aware that it might also benefit them. Of course, it might not have benefitted them but they were aware that being HER2-positive meant their disease was more aggressive.”
Recruiting the patients
More than five thousand patients worldwide took part in the study, which ran for 10 years with repeated follow up checks. A total of 14 patients were from Wales, including seven taking part at the Singleton site.
Kim Shears, from Swansea, was one of those seven having been diagnosed with HER2-positive breast cancer aged 45.
Kim had surgery, chemotherapy and radiotherapy treatment and remembers being offered Herceptin as part of the HERA trial.
“I was a bit doubtful about taking part in the trial at first,” said Kim, “but I’m so thankful I did. I wanted to get fit and better and I wanted to give myself the best chance possible.
“Siân and the team talked me through the trial and the side effects of the drug, and I also did some research myself, and I decided that for me the benefits outweighed any risks.”
Herceptin was known to have potential side effects on heart function so patients within the study were regularly tested to make sure they didn’t have a major reaction.
As a research nurse, Siân supported the patients at every stage of the trial.
“Not only them,” said Siân, “but you tended to support their family as well, because the husbands came with them and some of these patients were quite young and in those days their children would come as well.”
Getting the results
Just 18 months into the trial, the first set of results came in and they showed that patients who had been on Herceptin for one year were benefitting greatly.
“When the first results of the HERA trial where published, they showed a 46 per cent reduction in the risk of recurrence for patients receiving Herceptin,” said Dr Gianfilippo Bertelli, the Principal Investigator for the HERA trial at Singleton. “It was too soon at that time to know the effects on the risk of death.”
“Because we knew that these patients were benefitting, we couldn’t let those patients who weren’t receiving the drug continue with standard treatment only,” recalled Siân.
“So, we asked them what they would like to do including whether they wanted just one year of Herceptin or to be randomised again to receive either one or two years of the treatment.”
All of the Singleton patients who were in the control arm of the study, not receiving any treatment, opted to have Herceptin for one year because the results of the two year treatment were still unknown at that point.
“It was quite exciting,” added Siân. “Of course the patients who were on the one year arm of the study were very happy about the fact that they’d been on it and the patients who were on no treatment, and were then offered it, were happy they could access the drug.”
“It was fantastic when the interim results came out, showing Herceptin was working,” said Kim, who was on the one year arm of the study. “You don’t realise the impact at the time, as you’re on a rollercoaster. So it was a few years after when I realised how lucky I was.”
The Herceptin hype
The initial results were widely published in the media and soon breast cancer patients were asking their doctors for Herceptin.
However, despite this early evidence it was working, the drug was still in a clinical trial so it hadn’t been licensed and couldn’t be prescribed.
Critically, most breast cancer patients are HER2-negative, which is less aggressive and more treatable. “So those patients will not benefit from having this at all,” said Siân. “It’s only a small group of HER2-positive patients who benefit from Herceptin treatment.”
“The issue that we had when it went in the papers was that patients didn’t really realise that they may not benefit from it so anybody who had breast cancer wanted this drug, whereas actually the majority of patients didn’t need it and they were better off not needing it.”
But even for those it might work for, there was no immediate access to the drug. “You may remember,” said Siân, “we had patients camping out in the Welsh Assembly in Cardiff wanting the drug because they knew they were HER2-positive but being outside of the study, they couldn’t get it.”
“There was certainly a public outcry for the drug but these things can’t be rushed. You can’t give people drugs that haven’t gone through that process to make sure they’re effective and safe.”
The impact of the HERA trial
In 2006, the National Institute for Health and Clinical Excellence (NICE) recommended that Herceptin should be made available on the NHS for all women with HER2-positive breast cancer, transforming survival rates. Today more than 8 out of 10 patients survive at least 10 years from diagnosis.
The HERA study paved the way for studies leading to Herceptin’s use in other forms of the disease, including cancer of the oesophagus.
Other trials have improved the way Herceptin is given.
“A small injection under the skin is now standard rather than giving the drug intravenously,” explained Siân. “It’s a much less distressing, quicker way that doesn’t need a hospital visit. That came from a follow on trial that we did here and that’s where Herceptin treatment in the NHS is now.”
The women who went before
All of the patients who took part in the trial at Singleton have been living disease-free for more than 15 years.
“It’s pretty remarkable isn’t it?” concluded Siân. “I’m really proud to have been part of the trial, especially as I was there from day one. All the treatments we have are because of people who have gone before and taken part in clinical trials.
“As nurses we are here to make a difference to people and make things better. This is a trial that has actually changed practice and has transformed what a HER2-positive diagnosis means for any woman and their loved ones.”
Following all phases of the HERA trial, one year of Herceptin is still the standard treatment for HER2-positive breast cancer patients in the early stages of the disease, following surgery, chemotherapy and in some cases radiotherapy, depending on the type of surgery needed.
Now 61, Kim has two daughters and a granddaughter.
“I just feel privileged to have had the drug – the wonder drug,” said Kim. “I believe it made a big difference to how long I’ve survived. I’m just glad I said yes! I also feel really proud that by taking part in the study I’ve been able to help other people as well.”