New insight into breast cancer risk after stopping HRT

The findings, published in The Lancet, suggest that all types of hormone replacement therapy (HRT) - besides topical vaginal oestrogen - used to treat menopausal symptoms are associated with an increased risk of breast cancer. This risk may persist for more than ten years after stopping HRT according to the researchers.

The analysis looked at data from over 100,000 women with breast cancer from 58 different studies worldwide carried out between 1992-2018. Besides topical vaginal oestrogens, all types of HRT were found to increase the risk of breast cancer in women. These risks were greater for women who use combined oestrogen-progestogen HRT than oestrogen-only HRT.

HRT) is used by around a million women in the UK to improve symptoms of menopause by replacing the oestrogen that stops being produced by the ovaries when a woman enters the menopause. Some forms also include the hormone progestogen.

The authors estimated the 20-year risk of breast cancer for those starting HRT aged 50. For average-weight women who have never used HRT the average risk of developing breast cancer is around 6.3 per 100 women. For women using oestrogen and daily progestogen HRT, the risk increases to 8.3 per 100 (an increase of 2 women per 100). For women using oestrogen and intermittent progestogen, the risk is 7.7 per 100. Oestrogen-only HRT has the lowest risk at 6.8 per 100 users.

The risk of breast cancer after HRT was discontinued depended on how long it had been used for. The increased risk of breast cancer doubles for women using HRT for 10 years rather than 5 years.

If HRT was used for five years, around half of the higher risk of breast cancer would be during the 5 years that it was being used, with the other half occurring over the next 15 years after HRT was stopped. For those using any type of HRT for less than a year, there was little risk after discontinuing use.

"Our new findings indicate that some increased risk persists even after stopping use of menopausal hormone therapy. Previous estimates of risks associated with use of menopausal hormone therapy are approximately doubled by the inclusion of the persistent risk after use of the hormones ceases," said co-author Professor Valerie Beral from the University of Oxford.

Whilst an important and useful analysis of the existing data on breast cancer and HRT, Professor Janice Rymer, consultant gynaecologist and vice president of the Royal College of Obstetricians and Gynaecologists (RCOG) reflected that these findings "do not add anything new in terms of the effects of hormone replacement therapy. Research shows that, for most women, HRT helps to manage menopausal symptoms and is safe."

The results should be weighed up to reflect greater risks to women worried about breast cancer when considering HRT treatment, said Rymer. "These findings should not put women off taking HRT if the benefits - such as protection of bones and decrease in cardiovascular risk - outweigh the risks.

"To put the risk into context, a woman has greater risk of developing breast cancer if she is overweight or obese compared to taking HRT. Women must be aware of the effect of obesity and alcohol which increase the risk of breast cancer and modifies the additional risk of HRT."

This was echoed by the British Menopause Society (BMS). Both organisations agree that the findings are useful to clinicians when informing women about their risk of breast cancer whilst using and after discontinuing HRT. "The overall findings from this study are in keeping with the NICE menopause guideline recommendations which show a small increase in risk of breast cancer with HRT. Women must be informed of the data on breast cancer risk with HRT to help them make an informed decision," said Mr Haitham Hamoda, Chair of the BMS.

The study was co-funded by Cancer Research UK. The findings on post-HRT breast cancer risk are an "insight into hormone replacement therapy (HRT) that we didn't have before", according to Dr Julie Sharp, head of health and patient information at Cancer Research UK.

"It's important to put the risk in perspective - HRT causes 1,400 cancers a year in the UK, which is less than 1% of cases. We need high-quality, accurate information on the long-term effects of using HRT, which is why we've funded this research; women have to know the risks of which type of HRT they take and how long they take it for to decide what's right for them. Anyone considering starting or stopping HRT should speak to their doctor."

This study was published in The Lancet.