HRT and breast cancer: how high are the risks?


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By Rod Tucker
Community pharmacist

10 Sep 2019

How should pharmacists talk to patients concerned with the side-effects of HRT? Rod Tucker reviews the evidence

With the current supply problems of hormone replacement therapy (HRT) products, it is perhaps worth exploring the risks and benefits associated with HRT.

The menopause is a normal phase in a women’s life that occurs at around 50 years of age and is associated with symptoms such as hot flushes and night sweats. These are common problems that can affect up to 75% of women and are due to the decline in the production of oestrogen. HRT contains either oestrogen alone (for those without a uterus, ie after a hysterectomy) or with an added progestogen when a women has an intact uterus, since unopposed oestrogen can cause overstimulation of the uterus lining, increasing the risk of uterine cancer.

In the past, observational studies suggested that HRT had a protective role in coronary heart disease, although the first randomised trial to study the impact of HRT on secondary prevention of coronary heart disease showed no benefit.

In more recent years, the impact on heart disease has been re-evaluated such that in guidance from NICE in 2015, it was recommended that HRT does not increase the risk of cardiovascular disease risk if started in women aged under 60 years of age. NICE guidance also indicated that HRT can reduce the risk of fragility fractures and is thus beneficial against osteoporosis.

 

Potential risks?

 

Nevertheless, media reports have emphasised the possible downside of HRT and, in particular, the increased risk of breast cancer. This was first observed with the use of combined HRT (ie, oestrogen and progesterone) in 2002 after publication of the Women’s Health initiative (WHI) study.

Further analysis from this study found that there were mixed results among women using only oestrogen. For instance, although there was a decreased risk of hip fractures, oestrogen replacement had no effect on coronary heart disease, reduced the risk of breast cancer but increased the risk of stroke.

The potential for an increased risk of breast cancer from using HRT was recently back in the news after the publication of a study in the Lancet. This included data from over 500,000 women from 58 studies and compared the risk of breast cancer in those who had used HRT to non-users.

The new study covered the period from 1992 to 2018 and included women who had been through the menopause naturally as well as those with a hysterectomy. A strength of this study was that the authors had access to individual patient data and recorded the age at which women started HRT, the duration of use and the type of HRT which had been used. The results showed that of women diagnosed with breast cancer at an average age of 65, 51% had used HRT.

The risk of developing breast cancer was found to be elevated for more than 10 years after stopping HRT but more importantly, the risk was also dependent on how long women had used HRT.

The study found that:

  • For women using HRT for five years, there would be an extra 20 cases of breast cancer per 1,000 women who used oestrogen and progestogen
  • For women using oestrogen-only HRT, there would be an extra five cases of breast cancer per 1,000 women.

To put this into context, it is estimated that there would normally be approximately 63 cases of breast cancer per 1,000 women aged 50 to 69 years. Using combined HRT for five years starting at age 50 would increase the 20-year risk of developing breast cancer from 6.3% to 8.3%, an increase of two cases per 100 women. Using oestrogen-only HRT for five years would increase the 20-year risk of breast cancer from 6.3% to 6.8% or an increase of one extra case per 200 women.

 

What next? 

 

So how should pharmacists advise patients who want to stop HRT in light of these new findings? Menopausal symptoms can be extremely debilitating and have a significant impact on a women’s physical and psychological wel-being and HRT is effective at managing these symptoms.

Despite the potential increased risk of harm from HRT, it was reassuring to find in an analysis of mortality from the WHI studies (which sparked the original controversy) that after a follow-up of 18 years, there were no differences in mortality for any cause (ie cardiovascular disease, cancer etc) between those using combined HRT or oestrogen alone.

The fact that HRT increases the risk of breast cancer has been known for many years and in responding to these new findings, the Royal College of Obstetricians and Gynaecologists said that for most women, HRT helps to manage menopausal symptoms and is safe.

It is important that women have access to the facts to enable them to make an informed decision as to whether to use HRT. The increased risk from HRT is small and has to be seen in relation to other lifestyle measures that increase the risk of breast cancer including obesity, alcohol consumption and lack of exercise.

Each of these factors can be easily modified and incorporated in a healthy lifestyle to minimise the overall risk of developing breast cancer. It is therefore important that this message is conveyed by health professionals to women whose concerns have become too narrowly focused on the risk of breast cancer risk from HRT.


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