Behind the Headlines

Thursday February 5 2009

HRT is a treatment used to replace hormones in the body

Within a year of stopping hormone replacement therapy (HRT) a woman’s risk of breast cancer is almost back to normal, The Daily Telegraph reports. It says a new study has provided strong evidence that HRT causes breast cancer and that “women who take HRT for more than five years double their risk of suffering breast cancer for every 12 months they spend on the therapy”.

This new study is based on the original Women’s Health Institute (WHI) trial, which was stopped early in 2002 when it found that combined HRT (oestrogen and progestogen) increased the risk of breast cancer, blood clots and strokes. This new study looked at what happened to the women enrolled in this trial after they stopped taking HRT.

As reported in the news, the study provides direct evidence that the breast cancer risk reduces quickly after stopping HRT. It also strengthens the case that HRT is a causal factor for breast cancer and can increase risk when taken long term.

Where did the story come from?

Dr Rowan T Chlebowski from the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical
Centre, California and colleagues from across the US carried out the research.This current study was based on an earlier 2002 trial: the Women’s Health Institute (WHI) trial.

The original trial and this study were supported by grants from the National Heart, Lung and Blood Institute. The study was published in the peer reviewed journal The New England Journal of Medicine.

What kind of scientific study was this?

In this cohort study, the researchers investigated what happened to the women who had taken part in the 2002 WHI trial. This original trial was stopped early when the health risks were found to be greater than the benefits of continuing the study. They were also interested in another observational study that had similar entry criteria to the WHI trial.

In 1993, the WHI trial enrolled over 16,608 women between the ages of 50 and 79 years who had been through the menopause. The women were free of other illnesses such as a history of invasive breast cancer or hysterectomy. They had a mammogram at the beginning of the study and a clinical breast examination to ensure that they did not already have breast cancer. The women were asked not to use HRT for three months to ensure their bodies were free of the drug. After this wash out period, the researchers randomly allocated the  women to receive either a daily dose of HRT (conjugated equine estrogens (0.625 mg) with medroxyprogesterone acetate (2.5 mg)) or placebo.

Over 15,000 women who took part in the WHI trial did not develop breast cancer and had data available for analysis. The current study focused on these women.

The researchers decided also to use data from another observational study in their analysis. This second study had similar entry criteria but the participants were not randomised. Instead, it followed over 40,000 women from 1994 to 2005. These women had not had a hysterectomy or breast cancer and had had normal mammograms obtained within two years of the study.

When asked, 25,328 women said they had not used menopausal hormone therapy and 16,121 said they were using oestrogen and progestogen. This study did not instruct the women on whether or not to take HRT, but did inform them of the results of the WHI trial.

All the women were followed up to see how many developed breast cancer and the results were analysed separately.

What were the results of the study?

The researchers say that the HRT and placebo groups in the WHI trial had similar risk factors for breast cancer. Despite this, women taking HRT were found to have an increased risk of invasive breast cancer. There were 199 cases versus 150 cases in the placebo group (HR 1.26; 95% CI 1.02 to 1.55). Although in the first two years of the trial there were fewer cases of breast cancer in the treated group, overall this risk increased over the five years that the women were on HRT. The elevated risk decreased quickly after both groups stopped taking the study pills despite a similar frequency of mammography.

The groups in the observational study were not as well matched, and those taking HRT were more likely to be more active, white, younger and non-smokers. The rates of breast cancer were relatively stable until 2002 when the annual adjusted rates decreased in a similar pattern. From 2002 to 2003 these fell from 122 cases to 68 cases.

What interpretations did the researchers draw from these results?

The researchers say that their analysis of the two studies together gives a picture of the influence of this type of HRT (oestrogen plus progestogen) on “the incidence of breast cancer and breast cancer detection”.

In the clinical trial, they say that although breast cancer diagnosis in the HRT group was initially lower than in the placebo group, this may have been due to the difficulty of detecting breast cancers in women on HRT.

The researchers say that the rate of newly diagnosed breast cancer in the observational study was about “twice as high among women who used hormones as among those who did not use them”. They explain that this finding probably reflects the longer time that these women had been taking HRT compared with the women in the clinical trial.

They also say that the rapid decrease in breast cancers after women were made aware of the risks in 2002 cannot be explained by differences in the use of mammography.

What does the NHS Knowledge Service make of this study?

As expected, most women stopped taking HRT after the results of the WHI were published. Only 4% of women enrolled in the WHI reported using HRT a year after being instructed to stop taking it. This means that there were still small numbers of women taking HRT two years after the end of the WHI trial to make a comparison with.

The researchers also acknowledge that the decreasing rates of breast cancer over time could be due to factors other than stopping HRT. There may also have been differences in how the use of hormone-therapy was assessed and in the number of times women had mammography over the period of observation. In this study, however, there was only a 2% difference in mammography use between groups, and this suggests that this was not an important factor.

Overall, this study demonstrates a reducing risk of breast cancer in women who stopped HRT. As such, it confirms suspicions that the small increase in breast cancer risk in women taking both oestrogen and progestogen long term is caused by these hormones.

Links to the headlines

HRT cancer connection 'confirmed'. BBC News, February 05 2009

Risk falls after year off HRT. The Sun, February 05 2009

Taking HRT for five years 'doubles breast cancer risk every year'. The Daily Telegraph, February 05 2009

Links to the science

Chlebowski RT, Kuller LH, Prentice RL, et al. Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women. NEJM 2009; 360:573-587

Further reading

Farquhar C, Marjoribanks J, Lethaby A, Suckling JA, Lamberts Q. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2005

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Analysis by Bazian

Edited by NHS Choices