New study provides clearer picture on breast cancer risk and HRT use

A new study, led by experts at the Universities of Nottingham and Oxford, provides a clearer and more detailed picture on which women are at increased risk of breast cancer when using different HRT treatments.

The results of the study, published in The BMJ, confirm that HRT use is associated with increased risks of breast cancer, particularly for older women. However, it also suggests that for longer term HRT use the increased risks are lower than those reported in a recent meta-analysis, which combined the results of 24 varied studies.

The study also shows a more noticeable decline in increased risk once HRT has stopped, again when compared to the same meta-analysis.

Hormone replacement therapy (HRT) can be a significant benefit to women who suffer severe symptoms during menopause. Up to 80% of women experience some unpleasant symptoms such as hot flushes, night sweats, mood changes or memory and concentration losses. Osteoporosis is also associated with menopause and, for a small proportion of women, symptoms can be disabling and affect their quality of life.

HRT treatments involve one or more of a class of hormonal drugs, with an oestrogen as the key component and a progestogen normally added to protect the womb. As with all drug treatments, HRT has side effects and an increase in risk of breast cancer is one these.

Whilst previous studies have looked at associations between HRT use and increased risks of breast cancer, the detailed evidence of the risk associations with hormones used in specific HRT treatments has been lacking.

Dr Yana Vinogradova, a Senior Research Fellow in the School of Medicine at the University of Nottingham is lead investigator on the study. She says: “Our purpose was to conduct the largest observational study ever undertaken, and to include all available information on HRT use and other risk factors. Our aim was to provide comprehensive, detailed and accurate estimates of the risks for different HRT treatment formulations.”

To carry out the study, the team extracted data over a twenty period between 1998 and 2018 from two of the largest UK primary care databases, covering 2000 GP surgeries. The team identified all women aged from 50 to 79 with a diagnosis for breast cancer, matching by age and general practice to controls with no breast cancer diagnosis. They then compared the HRT prescription records of all women who had developed breast cancer with those who had not, taking into account when and for how long patients had been using a treatment.

To investigate the relative safety of different treatments, all HRT treatments were included, with the hormones used in the treatments and the method of delivery (tablets, patches or creams) all being investigated.

The results showed that the increased risk of breast cancer was much higher for combined oestrogen-progestogen treatments than for oestrogen-only treatments. Risk also increased the longer patients used HRT. The increased risks diminished when HRT treatment stopped, disappearing completely for oestrogen-only users and for short-term users of combined treatments.

Our study has found that the level of increased breast cancer risk associated with HRT depends on a number of factors, which can be reduced by careful choice of treatment. This will be of particular benefit to women in their 70s, for whom the levels of increased risk are highest. Many women, however, may be reassured by the low levels of associated increased risk of breast cancer for them from the treatment they are using. These results provide clearer, more detailed, and more robust information for doctors and patients about the relative increases in risk of breast cancer for all HRT treatments used in the UK. They should both facilitate and increase confidence in treatment choices, and be useful in the development of best-practice guidelines

The study was funded by the NIHR SPCR.

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