Thirty years ago, Lesley Laxton, a 53-year-old dentist from Colchester, received an invitation to attend a routine NHS breast screening. Alongside the invitation was a letter from Professor Dame Valerie Beral asking her to participate in a new study investigating the links between hormone replacement therapy (HRT) and breast cancer risk.
At the time, more and more women in the UK and elsewhere were taking HRT to relieve menopausal symptoms amid claims it could improve their general wellbeing and life expectancy. But emerging evidence from small studies suggested that HRT might increase women’s risk of breast cancer.
In search of some definitive data, Beral and her team at the Oxford Cancer Epidemiology Unit (now part of Oxford Population Health) set out to recruit a million women in their 50s and early 60s who they could track for a number of years through regular questionnaires and NHS records. Between 1 May 1996 and 2001, some 1.3 million women – a quarter of all UK women between 50 and 64 – filled in the recruitment questionnaire and brought it to their breast screening appointment. Among them was Laxton.
‘I was happy to participate,’ she recalls. ‘It was of interest to me because we were a generation of women that had started taking HRT, and there was a lot of misinformation going around. It was not clear whether it was a good thing or a bad thing.’
Like other women in the study, Laxton had grown up in the 1950s and come of age in the 1960s at a time of enormous change for women. ‘We were very conscious of the fact that we were different from our parent’s generation and had different expectations from our lives. There was more freedom – it was the beginning of the pill and so on.’
As well as looking at the associations between HRT use and breast cancer risk, the Million Women Study would provide the first opportunity to investigate how changes in behaviour and lifestyle had affected the long-term health of this generation of women.
As most diseases become more common after middle age, the researchers also understood the value of targeting this age group of women, recalls Professor Gill Reeves, the current Director of the Cancer Epidemiology Unit, who was working as the study’s statistician at the time.
Landmark findings on HRT
In 2003, Beral and her team published their first major findings from the study in The Lancet. The results showed that women taking combined oestrogen and progestogen HRT were at twice the risk of developing breast cancer compared to non-users, while those taking oestrogen only HRT had around a one-third higher risk.
The authors estimated that the use of HRT by women aged 50 to 64 in the UK over the previous decade had resulted in 20,000 additional breast cancers.
The findings made headlines in the UK and around the world and, along with similar results from smaller studies, dramatically changed attitudes towards HRT. Clinical guidelines also changed in response to the findings and women were advised to take HRT for shorter periods, or not at all if they were at high risk of breast cancer. As HRT use fell in many countries, the incidence of breast cancer in women over the age of 50 also decreased.
Further results from the study revealed that HRT slightly increased women’s risk of ovarian cancer and that oestrogen-only HRT increased the risk of endometrial (womb) cancer in post-menopausal women who had not undergone a hysterectomy.
In recent years, HRT use has once again been on the rise among UK women and there is increasing public discussion about the risks and benefits of the next generation of hormonal therapies.
Answers to other questions
Over the following years, Laxton filled out detailed questionnaires that arrived in the post, and later by email, on various topics, including her diet, levels of physical activity, drinking and smoking habits, and even how the COVID-19 pandemic had affected her physical and mental health. Her responses and those of the other participants provided the research team with a wealth of data about the impact of numerous factors affecting women’s risk of different diseases, including cardiovascular disease, many different types of cancer, liver cirrhosis, thrombosis and motor neurone disease.
In 2018, the study team began recruiting for a participant panel that would give women taking part in the research the chance to share their perspective on issues they had direct experience of, including conditions associated with ageing such as disability, stroke and dementia.
Co-Principal Investigator Sarah Floud recalls the ‘enthusiastic response’ from participants and the excitement of meeting for the first time some of the women who had made the research possible. ‘It was so inspiring to meet the participants, as the only contact we had before was through their questionnaires or if they rang our helpline.’
Laxton was among 15 women selected to serve as a ‘sounding board’ for decisions such as what questions to include in surveys, how findings should be shared, and future directions for research.
‘I was on the panel for four years,’ she says. ‘We explored so many things – diet, physical activity, neurodegenerative diseases.’
A resource for years to come
Thirty years after joining the study, Laxton, now 83, continues to take an active interest and currently serves on its advisory committee. She reflected, ‘I’m very proud of having participated in something that was ground-breaking. The research must continue.’
The sheer size of the Million Women Study means it continues to generate data on many aspects of women’s health from risk factors for rare medical conditions to more common diseases of old age. None of this would be possible without the willingness of women like Laxton to share so many details of their lives, says Floud.
‘We would like to thank every woman who has taken the time to fill out our questionnaires and provide blood samples when asked,’ adds Reeves. ‘Their data are invaluable and will continue to be invaluable to researchers for many years to come.’