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Study suggests HRT carries higher risk of breast cancer than thought

Tuesday 3 September 2019

"Breast cancer: Menopausal hormone therapy risks 'bigger than thought'," BBC News reports.

Hormone replacement therapy (HRT) is taken to relieve menopausal symptoms such as night sweats and hot flushes.

But it's long been recognised that HRT is linked to an increased risk of breast, womb and ovarian cancers, as well as the risk of cardiovascular problems such as blood clots.

New research has gathered data from 58 studies that included around 500,000 postmenopausal women, and compared the risk of breast cancer among those who took HRT and those who did not.

It found more than 1 year's use of HRT increased the risk of breast cancer, with the risk increasing the longer HRT was used.

Women appear to remain at increased risk more than 10 years after they'd stopped taking HRT.

The risk was greater with combined oestrogen and progestogen HRT than oestrogen-only HRT.

To put this into context, 63 out of 1,000 women aged 50 to 69 develop breast cancer. The use of combined HRT for 5 years would cause an extra 15 to 20 cases per 1,000.

The Medicines and Healthcare products Regulatory Agency (MHRA), which regulates the safety of medical products in the UK, has advised women concerned about the news to talk to a GP.

It's fine to stop taking HRT, but doing so gradually is best to stop symptoms coming back.

The study also highlights the importance of attending breast cancer screening appointments.

Where did the story come from?

The study was carried out by researchers who were part of the Collaborative Group on Hormonal Factors in Breast Cancer.

Funding was provided by Cancer Research UK and the Medical Research Council.

It was published in the peer-reviewed journal The Lancet and the study can be read online for free.

UK media reporting of the study was generally accurate and responsible, but many of the headlines were not particularly informative or useful.

Being told that a risk has "tripled" (as the Mail Online reported) does not mean much if you did not know what the initial risk was in the first place.

What kind of research was this?

This study gathered patient data from observational cohort studies that followed postmenopausal women who'd taken HRT, and looked at breast cancer outcomes.

The collaborative research group has regularly kept track of both published and unpublished studies of women taking HRT since 1992 through automated computer searches, manual searches of literature, written communication and meetings with experts in the field.

Though randomised controlled trials are the most reliable way of looking at the effectiveness of treatments, observational cohort studies are often used to gather information on potential harms.

They have the advantage that they can follow much larger numbers of women over much longer periods of time than could be achieved through a trial.

The research group focused on identifying studies that included more than 1,000 women to give a reliable indication of possible effects.

What did the research involve?

The research group identified 58 studies from 1992 to the present day comparing women who'd used HRT with those who had not.

All studies included women who'd been through the menopause, either naturally or as a result of hysterectomy and ovary removal.

The researchers gathered individual patient information on sociodemographic status, reproductive history and body measurements.

They looked at the age women started HRT, duration of use and the type of HRT used.

For women who developed breast cancer, they looked at the date they'd developed breast cancer and used the same date for comparison in age-matched controls who had not developed breast cancer.

They then compared the women's last reported use of HRT prior to this.

Women were considered to be "current users" of HRT if their last reported use was less than 5 years before cancer diagnosis, or "past users" if greater than 5 years.

The researchers analysed the results for all women and according to whether they were users of oestrogen-only or combined oestrogen and progestogen HRT.

What were the basic results?

The 58 studies included a total of 143,887 women who developed breast cancer and 424,972 women who did not develop cancer.

Women were diagnosed with cancer at an average age of 65, and 51% of these women had ever used HRT.

The researchers focused their analyses on 128,435 cases and 366,965 controls with the complete information available.

Current users

Women were said to be current users if their last reported use of HRT was less than 5 years before a diagnosis of cancer.

Current users of HRT had an increased risk of breast cancer if they'd used HRT for more than 1 year, and the risk increased the longer they used HRT.

The risk was seen for both oestrogen-only and combined HRT, though it was greater for combined HRT.

The main results for current users were:

  • 1 to 4 years use: oestrogen-only HRT 17% increased risk (relative risk [RR] 1.17, 95% confidence interval [CI] 1.10 to 1.26); combined HRT 20% risk (RR 1.20, 95% CI 1.01 to 1.43)
  • 5 to 14 years use: oestrogen-only HRT 33% increased risk (RR 1.33, 95% CI 1.28 to 1.37); combined HRT doubled risk (RR 2.08, 95% CI 2.02 to 2.15)

Risks were greater for oestrogen-receptor positive breast cancers, where oestrogen stimulates the growth of cancer cells.

Risks were seen for women starting at any age from 40 to 60 years.

Past users

Women were said to be past users if their last reported use of HRT was more than 5 years before a diagnosis of cancer.

There was a similar pattern of increasing risk for women who'd previously used HRT for more than 1 year.

But risk increases were mostly seen for women who'd taken HRT for longer than 5 years.

Many of the risks associated with HRT use for between 1 and 4 years bordered on statistical significance.

When analysing the results according to how long it had been since the women had used HRT, the increased risk remained for more than 10 years, and the risk increased the longer they'd used HRT.

Again, the increased risk seemed to be slightly greater for combined HRT rather than oestrogen-only HRT.

Both oral (tablet) and transdermal (skin patch) HRT were linked to risk, as were all types of progestogen or oestrogen used.

The only preparation not linked to increased risk was vaginal-only oestrogen.

How did the researchers interpret the results?

The researchers quantified the number of extra cases of breast cancer there would be in women aged 50 to 69 years who started HRT aged 50 and used it for 5 years.

These figures have also been reported by the MHRA.

To put this into context, about 1 in 16 women aged 50 to 69 develop breast cancer, or 63 per 1,000 women.

For women using HRT for 5 years, in this time there would be:

  • 1 case for every 50 users, equivalent to 20 extra cases per 1,000 women in those who took combined oestrogen, daily progestogen HRT
  • 1 case for every 70 users, equivalent to 14 extra cases per 1,000 women in those who took combined oestrogen, intermittent progestogen HRT
  • 1 case for every 200 users, equivalent to 5 extra cases per 1,000 women in those who took oestrogen-only preparations

10 years of use would double the number of cases.

Conclusion

The link between breast cancer and HRT has always been known, but this valuable research, based on a large volume of data, gives a better idea of how great those risks might be.

Using HRT for 1 year increases your risk of breast cancer, with a higher risk for longer use.

The risk appears to remain for more than 10 years after stopping HRT.

It also seems that there's a higher risk with combined preparations than with oestrogen-only HRT.

But HRT still has an important place in care. Menopausal symptoms can significantly affect the daily life and wellbeing of some women, and HRT is highly effective at relieving these symptoms.

Doctors need to assess the risks and benefits of HRT for each woman on an individual basis.

There are some risk factors, like having a history of breast cancer or cardiovascular disease, that prevent its use altogether.

If treatment is given, the type of HRT preparation used depends on a woman's symptoms, preferences and other risk factors.

This study found vaginal oestrogen creams were the only form of HRT not linked to breast cancer risk.

But creams can only help with symptoms like vaginal dryness. They do not help with other symptoms, like hot flushes and night sweats.

If HRT tablets or patches are prescribed, the MHRA emphasises that these should be used at the lowest dose and for the shortest amount of time needed to relieve symptoms.

If you're thinking about taking HRT for the first time, doctors will discuss your individual risk and options with you.

If you're currently taking HRT, the MHRA advises that:

  • a health professional discusses your risk with you at your next appointment
  • it's OK to stop taking HRT, but coming off gradually is best to try to stop symptoms coming back – a doctor can also advise about other ways to manage symptoms
  • all women should assess their breasts regularly, be vigilant for signs of breast cancer, contact a doctor if they see any changes, and attend screening appointments
  • you should discuss any concerns you have with a health professional

Analysis by Bazian
Edited by NHS Website