The research, published in The Lancet, is a combined analysis of data from 26 previous clinical trials of bisphosphonates, involving nearly 19,000 women. The results show that in women with early breast cancer who have gone through the menopause, bisphosphonates reduced the risk of dying from breast cancer after 10 years from 18% to 14.7% (a reduction of about one sixth) and the 10-year risk of breast cancer spreading to the bone from 8.8% to 6.6% (a reduction of about a quarter).
It might be easier to imagine two groups of 100 women. All women in both groups have been through the menopause and have since been diagnosed with early breast cancer. The women in the first group didn’t take a bisphosphonate drug for a period of time soon after they were diagnosed, whereas the women in the second group did. After 10 years, around nine women in the first group will have seen their breast cancer spread to the bone, and another 18 women will, sadly, have died from their breast cancer. In the second group, around seven women will have seen their breast cancer spread to the bone and a further 15 women will have died from their breast cancer.
The researchers estimate this means that bisphosphonates could potentially save the lives of around 1,000 women each year in the UK alone.
These landmark findings should change the gold standard of treatment for post-menopausal women with early breast cancer (also known as primary breast cancer). But what this highlights yet again is that we need to have a provision in the UK for licensing old drugs that have been proven useful for a new purpose, like bisphosphonates – something we’re campaigning for.
We’ve explained the story in full below but you can also watch Professor Rob Coleman, the clinical lead on the study, talk through these landmark findings.
What are bisphosphonates?
Bisphosphonates are, in simple terms, drugs that protect your skeleton. They do this by slowing the process that breaks down bone, and have been used for many years to treat conditions like osteoporosis. They generally have few side effects and healthcare teams know how to manage side effects if they do appear.
But for the last 20 years or so, bisphosphonates have also been used to limit bone damage in people living with cancer that has spread to the bones, and to counteract the bone weakening side-effects of some breast cancer drugs.
Old drugs, new tricks
For a long time, breast cancer clinicians who were prescribing bisphosphonates for their patients suspected that the drugs were doing more than just strengthening bones.
This suspicion was backed up by research studying the effects of the drugs in mice, which led to clinical trials to test whether bisphosphonates had any effects on breast cancer spread and patients’ chances of survival. But frustratingly the outcomes of these studies have been quite varied, with some showing benefits in only certain groups of patients.
Strength of evidence
With the aim of revealing a definitive answer, an international group of researchers have now brought together data from 26 international randomised controlled trials, involving nearly 19,000 women in total, and reanalysed all this information in its entirety.
Their huge analysis found that in post-menopausal women with early breast cancer, after a period of 10 years, bisphosphonates had reduced the risk of breast cancer spreading to the bone from 8.8% to 6.6% (a reduction of about a quarter) and the risk of dying from breast cancer from 18% to 14.7% (a reduction of about one sixth).
Interestingly, the benefits were similar irrespective of whether the cancer was hormone-positive, had spread to the lymph nodes, and whether the women had received chemotherapy.
In pre-menopausal women bisphosphonates didn’t seem to have any benefits in survival or stopping the disease spreading, but there were no additional harms from the drugs either.
It’s important to note that as all the data in the meta-analysis relate to bisphosphonates started at, or soon after, diagnosis, there is no clear evidence that patients who have already undergone treatment will benefit from starting additional treatment with bisphosphonates.
What happens next?
The researchers estimate that if every post-menopausal woman diagnosed with early breast cancer in the UK each year - around 34,000 - took a bisphosphonate for 3-5 years, after 10 years around 1,000 more of these women would still be alive.
This is an incredible opportunity, and with the strength of this evidence we want to see bisphosphonates made available as a treatment for every newly-diagnosed post-menopausal woman with early breast cancer who could benefit.
However, there is a hurdle in the way of progress. Although bisphosphonates are incredibly cheap, costing less than 5 pence a day per patient, their design and production is no longer covered by a patent, making it unlikely that a pharmaceutical company will provide the co-ordination and sponsorship to apply for a licence for this new purpose and ensure that they are adopted on the NHS as a treatment for breast cancer.
Unlocking off-patent drugs
Without a licence to act as a ‘kitemark’ of safety for a treatment, and a NICE technology appraisal to give the NHS a mandate to provide it, there are disincentives to bisphosphonates being prescribed as a treatment for breast cancer, which could result in them not being routinely available.
Bisphosphonates are not the only drugs that the off-patent issue effects and neglecting the potential power of off-patent drugs seems like a huge oversight to us.
That is why we’ve been campaigning on this issue. Last year we significantly raised the profile of the lack of availability of repurposed off-patent drugs in Parliament, by supporting former MP Jonathan Evans to introduce the Off-patent Drugs Bill. Although the Government chose not to support the Bill that time, on 24 June this year, we supported newly-elected MP for Torfaen, Nick Thomas-Symonds, to re-introduce a refined version of the Off-patent Drugs Bill which could become law in 2016 if it receives enough support from MPs.
The Bill would put into UK law a duty on the government to step in where there is no incentive for a pharmaceutical company to act, and act in the public interest to seek to license and approve off-patent treatments for use on the NHS
Bisphosphonates and Breast Cancer Now
The results of today’s study are just one example of why it’s so important to continue to research alternative uses for existing treatments as well as search for new ones.
At Breast Cancer Now we’re committed to understanding how breast cancer spreads to the bone, and how we can stop the disease spreading in as many patients as possible with bisphosphonates and other drugs. One of our researchers investigating bisphosphonates is Professor Ingunn Holen at the University of Sheffield - watch her talk about her work in the video below.
Ultimately, we believe that by bringing together research like Professor Holen’s and our campaigns to ensure patients benefit from research as soon as new results emerge, we truly can stop women dying of breast cancer by 2050.