A new study published today by the BMJ provides new estimates of the increased risk of breast cancer associated with the use of various HRT (hormone replacement therapy) supplements in the UK.

It confirms that the use of HRT is linked to an increased risk of breast cancer, especially in older women. However, it suggests that longer-term use of HRT, the increased risks are lower than in a recent meta-analysis that summarized the results of 24 studies.

Today’s study also shows a more marked decrease in the risks after stopping HRT compared to the same meta-analysis.

HRT is used to relieve menopausal symptoms such as hot flashes and night sweats. Treatments include tablets that contain only estrogen or a combination of estrogen and progestin, as well as patches, gels, and creams.

Previous research has shown that long-term use of HRT tablets is linked to an increased risk of breast cancer, mainly due to progestins.

Last year, a large meta-analysis reported a higher than expected breast cancer risk associated with HRT, but uncertainty remains about the risks associated with different types and durations of HRT.

So researchers at Nottingham and Oxford Universities set out to assess the differences in breast cancer risk associated with each of the hormonal components used in HRT.

They used two UK primary care databases (QResearch and CPRD) linked to hospital records to compile HRT prescriptions for 98,611 women aged 50 to 79 who were diagnosed with breast cancer between 1998 and 2018, compared to 457,498 women of the same age and to compare the same general medicine that did not develop breast cancer.

They analyzed the risks according to HRT type (only estrogen and combined estrogen and progestin therapy), according to recent (1-5 years) and previous (5 or more years) use, and according to short-term (less than 5 years) and long-term ( 5) years or more) use.

Other relevant factors such as smoking, alcohol consumption, pre-existing illnesses (comorbidities), family history and other prescribed medications were taken into account.

A total of 33,703 (34%) women with a diagnosis of breast cancer and 134,391 (31%) control subjects had recently or previously used HRT.

Risk increases were mainly associated with estrogen-progestin treatments, but small increases were also associated with estrogen treatments.

For example, long-term users recently had a 15% increased risk of developing breast cancer compared to an unused application for estrogen therapy only, while combined estrogen and progestin therapy had a 79% increased risk.

Long-term use of estrogen therapy in the past and short-term use of estrogen-progestin in the past were not associated with an increased risk. However, the risk associated with long-term use of estrogen and progestin in the past remained increased (16%).

To put these risks into context, newer estrogen users would expect between three (in younger women) and eight (in older women) additional cases per 10,000 women-years and for estrogen-progestin users between nine and 36 additional cases per 10,000 women-years.

For previous estrogen-progestin users, the results suggest two to eight additional cases per 10,000 women-years.

This is an observational study so no cause can be established, and the researchers point out some limitations that may have affected the accuracy of their results.

However, they say this was a large study using consistent sources of data from the “real world” primary care data. The results were similar upon further analysis, suggesting the results stand up to scrutiny.

In this respect, this study confirms that exposure to most HRT drugs is linked to an increased risk of breast cancer and that the risk levels vary between HRT types, with the risk being higher for combined hormonal treatments and for longer periods of use.

However, the results also suggest a lower increased risk of breast cancer associated with longer-term use of HRT and a greater decrease in risk after stopping HRT, somewhat counterbalancing the higher-than-expected risks reported in the recently published meta-analysis.

“Our results add further evidence to the existing knowledge base and should help clinicians and women identify the most appropriate HRT formulation and treatment regimen, and provide more consistently derived information for women health professionals, health researchers and treatment policy professionals,” they conclude .

HRT tablets are associated with an increased risk of blood clots

More information:
Use of hormone replacement therapy and breast cancer risk: nested case-control studies using the QResearch and CPRD databases, BMJ (2020). DOI: 10.1136 / bmj.m3873 Provided by the British Medical Journal

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