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Menopausal hormone therapy and breast cancer – Expert reaction

A large international study has found all forms of menopausal hormone replacement therapy, except topical estrogen creams, were linked to an increased risk of breast cancer.

The findings are based on data from 58 epidemiological worldwide studies that recorded menopausal hormone therapy use (MHT), then monitored rates of breast cancer, with more than 100,000 women developing breast cancer after MHT.

The rate of breast cancer was 6.3 per cent in women who had never used hormone therapy, rising to 8.3 per cent in those who had used a combination therapy (estrogen and progestogen) for five years. Women who had stopped using MHT had an elevated risk of breast cancer for 10 years after therapy stopped, although their risk was lower than women who were still using it.

The SMC gathered expert comment on the study, which is available on Scimex for registered journalists.

Professor Andrew Shelling, Associate Dean of Research, Faculty of Medical and Health Sciences, University of Auckland, comments:

“This large study describes that current and recent users of menopausal hormone therapy (MHT) are at an increased risk of breast cancer. While this known risk is small, the increase is significant. Balancing the amount of increased risk of breast cancer (and other disease risk), compared to the benefits to women with menopausal symptoms, is a difficult and important conversation.

“What this new study provides us, that looks at over 100,000 postmenopausal women with breast cancer, is the impact of different types of MHT and the length of treatment. It shows that the risks of breast cancer are higher for combination therapy (estrogen and progestogen) than estrogen-only therapy. Most importantly, the study describes that outcomes for women are related to the amount of time they were taking MHT. The study clearly shows that there is little increased risk of breast cancer if MHT is used for less than a year, but risk significantly increases with the duration of treatment.

“This new information will benefit discussions around the use of MHT in women with menopausal symptoms. While MHT remains an appropriate treatment for women with moderate to severe menopausal symptoms, it must now be considered that it is best to provide an appropriate MHT, for the shortest period of time necessary to control symptoms.”

No conflict of interest.

Professor Cindy Farquhar, Professor of Obstetrics and Gynaecology, University of Auckland, comments:

What did the researchers do? 

In the first study they have undertaken an individual participant meta-analysis of the worldwide data of women on MHT and combined all the results. As a result the study is the largest with the longest follow up and also has the most detailed information about risks with the length of treatment and types of hormone therapy and different age groups and if the effect goes on after stopping treatment. In the second study they have reported the long term analysis of the MWS on BC mortality.

What did we already know? 

“We already knew that MHT using estrogen and progesterone HT was associated with increased risk of breast cancer and that the risk was greater for >5 years use. Estrogen alone was thought to be safer with little or no change in the risk of breast cancer. And moderate term use up to 4-5 years was also thought to be relatively safe.

“We also knew that mortality from breast cancer was not increased among postmenopausal women in the Women’s Health Initiative study (the largest randomised study in this new analysis) who took combination MHT for a median of 5.6 years. Taking estrogen alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.

What does this study add?

“There is no increased risk of breast cancer with MHT use only if women use it for less than one year. While this is reassuring – as MHT can be used for short term management of menopausal hot flushes – it does mean that treatments longer than one year need to be considered carefully.

“The study also provides some details about risks for different ages and risks persisting after stopping. Starting MHT after the age of 60 appears to be safer but only for those women taking estrogen only.

“The study also reports that, in Western countries, there have been 20 million breast cancers diagnosed since 1990, of which 1 million would have been caused by MHT use. This means that 5 per cent of breast cancers could have been avoided.”

What are the implications for women?

“Women on MHT should talk to their doctors about their risks of breast cancer (other risk factors are high BMI, increased alcohol intake, family history). Making sure that they are up-to-date with their mammogram (every two years) would be one step. A second step would be to assess their need for MHT by stopping and seeing if they still have a need for it – hot flushes usually resolve over time. It is safe to use MHT short term if hot flushes make you miserable but don’t use if for long (one year in this case).”

No conflict of interest.