London School of Hygiene & Tropical Medicine

The findings use data from more than 100,000 women with breast cancer from 58 epidemiological studies worldwide, and suggest that all types of MHT, except topical vaginal oestrogens, are associated with increased risks of breast cancer, and that the risks are greater for users of oestrogen-progestagen hormone therapy than for oestrogen-only hormone therapy.

What does this research add to our existing understanding of the relationship between MHT and breast cancer? And what are the relative risks for women? Stephen Evans, Professor of Pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said:

“This is a report of a mammoth task to bring together the individual data from 58 studies involving 568859 women from many different countries.

“It shows some findings that are generally accepted now and some that are new. The accepted findings are that MHT can cause an increased occurrence of breast cancer in users who take it for more than 5 years and there is a higher risk in those who take it for more than 10 years. There is already good evidence that, while oestrogen combined with a progestagen reduces the risk of endometrial cancer compared with oestrogen-only MHT, the combination has a higher risk than oestrogen only MHT for breast cancer which outweighs the benefit of endometrial cancer risk reduction.

“The new findings are principally 1) that even in years 1 to 4 of use, MHT confers a risk of breast cancer though this risk is smaller than that with longer use; 2) the increased risk that is strongly dependent on duration of use has a “carry-over” effect which also depends on duration of use and lasting possibly 10 or 15 years after stopping; 3) there are clear differences between the different types of MHT, with topical vaginal oestrogens having the lowest risk and possibly conferring no extra risk; 4) the overall implications of both the evidence of risk prior to five years of use and the extent of the “carry-over” after use has ceased suggests that the overall role of MHT in breast cancer incidence is greater than thought previously.

“All these remarks assume that it is MHT that is the causal factor. The authors have used data on individuals to try and ensure that users and non-users were as similar as possible given their data. Similarity would only be guaranteed using randomised allocation to MHT. Their data are compatible with the randomised data which is much smaller in extent and has only been able to examine a very much smaller number of women starting MHT at the time of the menopause. The authors essentially note limitations of observational data; that the design of the studies cannot be as sure of the results as they could be if randomised. The great consistency shown in the findings do make it much more likely than not that these effects are causal.

“Some of the data will have related to products no longer in current use, but the evidence is consistent about what differences make a difference (mainly addition of a progestagen in combined MHT, and longer duration of use).

“The authors do a very good job in translating their results into numbers of practical use. Their interpretation is cautious but clear. These results should not be used to cause alarm among women, but there is no doubt that they should follow the advice given by the MHRA in the UK and the FDA in the US that MHT be used for the shortest time that it is needed. MHT does offer real benefits for menopausal symptoms, but its use beyond one year seems to confer a steadily increasing risk of breast cancer with increasing years of use.

“Breast cancer is in many cases a very treatable disease, but the accompanying research letter, based only on data from the UK Million Women Study, shows that the same pattern of risk – increases with increasing duration of use and addition of a progestogen – also applies to deaths from breast cancer which are rarer than the incidence of breast cancer.

“This is a “tour de force” in what has been done and the way it has been done – the findings cannot be dismissed.”