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HRT and Breast Cancer Risk Position Statement

A joint statement has been issued by the British Menopause Society, the International Menopause Society, the European Menopause and Andropause Society, the Royal College of Obstetricians and Gynaecologists and the Australasian Menopause Society on menopausal hormone therapy (MHT) and breast cancer risk in response to EMA Pharmacovigilance Risk Assessment Committee recommendations in May 2020.

Please find a summary of the Statement below.

The full Statement can be found here: https://thebms.org.uk/2020/09/hrt-and-breast-cancer-statement-in-response-to-ema-pharmacovigilance-risk-assessment-committee-recommendations-in-may-2020/

Summary of the HRT and Breast Cancer Risk Position Statement

Menopausal symptoms

The menopause transition can have a significant impact on many women, with more than 75% experiencing menopausal symptoms, a quarter describing severe symptoms, and a third experiencing long-term symptoms.

Treatments 

MHT, compared with placebo, has been consistently shown to improve menopausal symptoms and overall quality of life and remains the most effective treatment for menopausal symptoms. For some women, MHT may not be suitable, and alternative treatments are available.

MHT and breast cancer risk – the CGHFBC meta-analysis

Results from the CGHFBC meta-analysis show a small increase in the absolute risk of breast cancer:

5-years intake of MHT starting at the age of 50 years and risk of breast cancer at age 50-69 years

For continuous combined MHT
Increase from a baseline risk of 3/50 women not on MHT to 4/50 (i.e., 1 extra case in 50 women).

For sequential combined MHT
Increase from a baseline risk of 4/70 women to 5/70 (i.e., 1 extra case in 70 women).

For estrogen only MHT
Increase from a baseline risk of 13/200 women to 14/200 (i.e., 1 extra case in 200 women).

10-year intake of MHT starting at the age of 50 years and risk of breast cancer risk at age 50-69 years

For continuous combined MHT
Increase from a baseline risk of 3/50 women not on MHT to 5/50 (i.e., 2 extra cases in 50 women).

For sequential combined MHT
Increase from a baseline risk of 4/70 women to 6/70 (i.e., 2 extra cases in 70 women).

For estrogen-only MHT

Increase from a baseline risk of 13/200 women to 15/200 (i.e., 2 extra cases in 200 women).

Interpretation of the evidence on the risk of breast cancer with MHT 

The findings from the CGHFBC meta-analysis are in keeping with the NICE guidance 2015 analysis of the observational data on the risk of breast cancer and MHT.

The findings from the CGHFBC meta-analysis should be explained to women when discussing the benefits and risks of MHT. However, discussions on the risk of breast cancer with MHT should also include the findings from the WHI placebo-controlled randomized trials and the large E3N observational studies, which reported on the risk of breast cancer risk in users of micronized progesterone compared with other progestogens. Neither of the latter two studies was included in the CGHFBC meta-analysis.

The recently published WHI data showed a significant decrease in the risk of diagnosis of breast cancer with estrogen-only MHT and a significant reduction in breast cancer mortality compared with placebo. Women who took combined estrogen and progestogen MHT had an increased risk of breast cancer compared to placebo, in keeping with NICE guidance conclusions, but showed no significant difference in breast cancer mortality compared with placebo.

The E3N observational studies suggested a lower breast cancer risk in users of micronized progesterone compared to users of more androgenic progestogens.

Recommendations on the risk of breast cancer with MHT should take into consideration the findings from the WHI randomized trials and the observational data on micronized progesterone from the E3N study and those from the CGHFBC meta-analysis.

Informed consent

The risk of breast cancer should be considered in the context of the overall benefits and risks associated with MHT intake including menopausal symptom control, improved quality of life and the long-term impact on bone and cardiovascular health.

The decision whether to take MHT, the dose of MHT and the duration of its use should be made on an individualized basis after discussing the benefits and risks with women to help them make an informed choice about their health and care.

MHT benefits and risks

Quality of life

Key points summary

  • Menopausal symptoms affect 70-80% of all women.
  • 25% of women describe their symptoms as severe.
  • The average duration of menopausal symptoms is 7 years.
  • 50% of women said their symptoms impacted their home life and 36% said the menopause impacted their social lives

MHT and breast cancer risk - The CGHFBC meta-analysis

Key points summary:

  • Duration-dependent increase in the risk of breast cancer diagnosis with both unopposed estrogen and combined MHT.
  • The risk is higher with continuous combined MHT regimens compared to cyclical.
  • The risk of breast cancer remains elevated more than 10 years after discontinuing MHT.
  • No estrogen dosage effect on the risk of breast cancer with MHT.
  • Vaginal estrogen exposure did not increase the risk of breast cancer diagnosis.
  • Only a small number of women on micronized progesterone were included. Therefore, conclusions regarding its impact on the risk of breast cancer diagnosis could not be determined from this meta-analysis.

Osteoporosis

Key points summary

  • Evidence from RCTs and meta-analysis shows that women using MHT have a significant reduction in the risk of any fracture compared with women not using MHT.

Cardiovascular disease (CVD)

Key points summary

  • The timing MHT is initiated, referred to as the ‘timing hypothesis’ and ‘the cardiovascular window of opportunity’, can have a significant impact on the risk of CVD with MHT intake.
  • Cochrane data-analysis shows that MHT initiated within 10 years of the menopause is likely to be associated with a reduction in coronary heart disease and cardiovascular mortality.
  • Evidence from the Cochrane data-analysis and that from the long-term follow-up data of the WHI showed no increase in cardiovascular events, cardiovascular mortality or all-cause mortality in women who initiated MHT more than 10 years after the menopause.

Risk of venous thromboembolism

Key points summary

  • Compared with women not on MHT, the risk of venous thromboembolism is increased by oral intake MHT.
  • Transdermal administration of estradiol is unlikely to increase the risk of venous thrombosis above that in non-users and is associated with a lower risk compared with oral administration of estradiol.

Content created 18 August 2020