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Title Type and timing of menopausal hormone therapy and breast cancer risk
Date 30 August 2019
Full Story Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence
Collaborative Group on Hormonal Factors in Breast Cancer
thelancet.com Published August 29th 2019

This review of 58 observational studies, totalling 108,647 postmenopausal women who developed breast cancer, has confirmed the known association between use of Hormone Replacement Therapy (HRT), referred to as Menopausal Hormone Therapy (MHT) in this paper, and diagnosis of breast cancer. The publication confirms that obesity is an important risk factor for breast cancer, and provides further information about the effect of different regimens of HRT and of different progestogens. The highest risk was stated to be associated with the use of estrogen and daily progestogen (continuous combined or "period-free" regimen); followed by estrogen and cyclical progestogen (sequential or "monthly bleed regimen"); and to a lesser extent estrogen only. Of the progestogens used, dydrogesterone appeared to be associated with the lowest risk.

This information regarding varying effects of different regimens should be balanced with the knowledge that continuous combined regimens offer better protection from stimulation of the womb lining by estrogen, than sequential regimens. Estrogen only HRT should only be taken by women who have had a hysterectomy, so there is no womb lining present.

Women who commenced HRT before the age of 45 were analysed and compared to postmenopausal women younger than 45 who were not taking HRT. The increase in breast cancer for those younger women taking HRT should be interpreted with caution; having an early menopause (before age 45) decreases breast cancer risk and taking HRT until the average age of the menopause restores risk to approximately baseline risk for that woman had she not had an early menopause. Untreated early menopause increases cardiovascular and osteoporosis risk and is associated with increased risk of premature death.

While this publication provides important information, limitations do exist in relation to types of studies reviewed (with 43,022 cases from the much criticised Million Women study), and absence of data on mortality associated with breast cancer; previously reported randomised trials showing no significant difference in cancer deaths from women who took HRT compared to placebo.

The topic of use of HRT and development of breast cancer continues to be of great concern to both women and healthcare professionals. Any new research data should be taken into account when women are deciding what is the best option for them. It should be noted that the current belief is that HRT may stimulate the growth of breast cancer cells which are already present, rather than cause cancer, which may well have appeared at a later date had HRT not been taken. As always, individualisation is essential, balancing risks against benefits of symptom control and hence improved quality of life, heart health and bone health.

Women currently taking HRT should not feel that they are at significant risk and there is no need to urgently attend their GP practice for discussion. It is recommended already that when settled on HRT, women should have an annual review at their GP practice or Menopause clinic and discussion can take place at that time. This annual discussion should include assessment of benefits and risks so that a joint decision can be made about whether HRT is continued or not.

We welcome this further information provided by this publication, but it is clear that uncertainty still exists and well designed randomised trials are still needed to fully assess effects of different types of HRT.

For full article thelancet-press.com/embargo/HRT.pdf

The BMS response: see thebms.org.uk

The International Menopause Society comment: view pdf

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