One in a million – the story of the Million Women Study
1.3 million women recruited over five years. Two decades of follow-up. Hundreds of research findings.
It all adds up to the largest study of its kind in the world, and it’s all thanks to the team at the NDPH for making it happen – as well as all the women who have taken part over the years.
Back to the beginning
Back in the 1990s, there was relatively little known about the influence of hormone-based drugs on breast cancer risk. Some people believed that the contraceptive pill could increase the chances of developing the disease, and others were concerned about hormone replacement therapy (HRT) for treating menopausal symptoms.
HRT was becoming hugely popular thanks to media coverage of its benefit, and by the mid-90s around a third of menopausal women were taking some form of it. Yet few studies had been done looking in depth at whether it played a role in breast cancer risk.
In search of some answers, Professor Dame Valerie Beral and her team in the Oxford Cancer Epidemiology Unit (now part of the NDPH) decided to launch the biggest study of women’s health ever undertaken. Based on analysis of combined clinical trials by Professor Sir Richard Peto and his team, also in the CEU, Beral knew that to find reliable links between risk factors and disease – especially things playing a smaller role – she would need to look at as many women as possible.
A million women was a bold target, but it could be achieved thanks to the unique way in which participants were recruited. Originally set up with funding from the Imperial Cancer Research Fund (now Cancer Research UK), with subsequent support coming later from the Medical Research Council and the Health and Safety Executive, the Million Women Study has become a reality.
Making a million
Beral worked together with national cancer screening director Julietta Patnick to send out recruitment questionnaires alongside breast screening invitations for women in their 50s and early 60s, asking them to bring the completed forms back when they came for their appointment if they were keen to take part in the study.
Initially there was a concern that this might put women off coming for screening at all, but a pilot study showed that fortunately this wasn’t the case and around 70 per cent of women attending screening agreed to take part in the study. By making the process so simple, 66 screening centres recruited 1.3 million women over five years from 1996 to 2001 – a staggering one in every four women aged 50-64 across the whole of the UK.
Importantly, the data that women provided was also then linked to their NHS records, so the study team could follow them into the future. Initially, the questions focused on HRT in relation to breast cancer, but the study has expanded to become a vital window on women’s health in general. Beral and her research team also went back to the participants every three to five years to ask them for further information or to explore new questions.
The sheer size of the Million Women Study makes it incredibly powerful for picking apart the influences of everything from lifestyle to genes on health and disease. Perhaps its most significant finding was published in 2003, relating to the original aim of figuring out whether HRT plays a role in breast cancer risk.
After crunching through all the data, Beral and her team – notably statistician Professor Gillian Reeves – found that women who were currently using HRT were at an increased risk of breast cancer. This risk was significantly larger for women taking combined HRT containing the hormones oestrogen and progestogen, compared to oestrogen-only pills. Intriguingly, those who had used HRT in the past didn’t seem to have a higher chance of developing breast cancer, suggesting that a woman’s risk drops back down again once she stops taking it.
Since then, the Million Women Study has revealed that HRT can also increase the risk of ovarian cancer, while oestrogen-only HRT increases the risk of endometrial (womb) cancer. Taken together, breast, ovarian and womb cancer add up to 40 per cent of all female cancers in the UK, affecting many tens of thousands of women. Overall, over a five year period, for every thousand women not taking HRT, around 19 of them will develop one of these diseases. For 1000 women taking oestrogen-only HRT this goes up to 26, and up to 34 cancers for every 1000 women taking combined HRT.
Although they made major headlines in the UK and around the world, the team’s findings fitted with the results of similar smaller studies, including the 160,000-strong Women’s Health Initiative in the US (which was a clinical trial of HRT rather than an observational study like the Million Women Study). Due to the growing body of evidence around HRT and cancer risk, the guidelines for prescription have changed along with the information provided to doctors and patients. Today, HRT is only recommended to be taken for as short a time as possible to treat menopause symptoms, rather than prolonged use.
Since those first findings, many more important results have come out of the treasure-trove of data provided by the study, moving on from the initial questions about HRT, hormones and breast cancer risk.
For example, the study has provided reliable findings on the role of lifestyle factors and cancer – such as alcohol intake, height and weight, and smoking. As well as various types of cancer, Beral’s team are also investigating heart disease, hip fractures, arthritis, cataracts, dementia and motor neurone disease. And they’re looking at the impact of disability on attendance for cancer screening, as well as investigating the uptake of bowel screening in the study participants.
In 2016 alone, the Million Women Study team has discovered:
- Unhappiness and stress don’t directly cause ill-health or lead to early death – once lifestyle factors such as smoking were taken into account – although being in poor health can cause unhappiness.
- Being taller, having non-White ethnicity, and having asthma are risk factors for lung cancer in women who have never smoked tobacco. However, the increase in cancer risk from these factors is ten times smaller than that due to smoking.
- Female sterilisation (“tube-tying”) cuts the risk of some types of ovarian cancer, as well as rare cancers in the fallopian tubes and abdomen.
- Using the contraceptive pill for ten years cuts the risk of womb cancer by half. This is thought to have prevented around 400,000 cases of womb cancer worldwide over the past 50 years.
- Smoking, being obese and having diabetes increases the likelihood of needing surgery for cataracts, although a previous suspected link with HRT has been disproved.
The Million Women Study goes hand in hand with other large studies here in the UK and elsewhere around the world. For example, researchers at the NDPH are the driving force behind the UK Biobank, recruiting half a million men and women across the UK, as well as running the Oxford arm of EPIC – a study of lifestyle and cancer encompassing more than half a million participants across Europe – and the China Kadoorie Biobank, involving another half a million people across China.
Together, these studies are uncovering vital information about human health and disease. They are also starting to unpick the complex interactions between genes, environment, lifestyle and the risk of many diseases from cancer to dementia.
Most recently, data from the Million Women Study – along with information from the UK Biobank and EPIC-Oxford studies – was used to show that working night shifts (including long-term shift work) is not associated with an increased risk of breast cancer. They also combined these results with data from other large international studies to confirm that night shifts are not a risk factor for breast cancer, helping to settle a question that has been raised over several decades.
Finally, while Professor Beral is best known as the ‘mother’ of the Million Women Study, she is now taking on a new challenge in the form of AgeX – a study to find the most appropriate age range for breast cancer screening. Aiming to recruit around 3 million women from screening centres across England, it will be the biggest study of anything, anywhere in the world.
As with the Million Women Study and all the research projects that NDPH scientists are involved in, it’s only possible thanks to the participants who freely provide their time and information. We are grateful to each and every one of them.