SOME kinds of hormone replacement therapy (HRT) have a much greater effect on a woman's risk of breast cancer than others, according to landmark research published in the Lancet this Saturday (August 9).

The Million Women Study, funded by Cancer Research UK, the NHS Breast Screening Programme and the Medical Research Council, confirms that current and recent use of HRT increases a woman's chance of developing breast cancer and that the risk goes up with duration of use.

Current users of all types of HRT, including oestrogen-only, combined oestrogen-progestagen and tibolone, are at increased risk of breast cancer compared with women who have never used HRT. But the risk is substantially greater for users of combined preparations of HRT than for women on the other types.

Scientists at the Cancer Research UK Epidemiology Unit in Oxford analysed data from over one million women between the ages of 50 and 64. Women joined the study between 1996 and 2001 and half were using HRT or had done so in the past. The study included 9,364 cases of invasive breast cancer and 637 breast cancer deaths, registered over 2.6 and 4.1 years of follow-up respectively.

Researchers found that post-menopausal women using combination HRT were twice as likely to develop breast cancer as non users (a 100 per cent increase), while risk increased by 45 per cent among users of tibolone and by 30 per cent among users of oestrogen-only HRT. These effects were shown to wear off within a few years of ceasing use.

In developed countries, among 1,000 postmenopausal women who do not use HRT, there will be about 20 breast cancer cases between the ages of 50 and 60.

For every thousand postmenopausal women who begin 10 years of HRT use at age 50, there will be five extra cases of breast cancer among users of oestrogen-only HRT and 19 among users of oestrogen-progestagen combinations. So combined HRT causes four times as many extra breast cancers as oestrogen-only.

The study also found that current users have a 22 per cent increased risk of death from breast cancer compared with women who have never used HRT, although the result was of borderline statistical significance. It is too early to estimate the number of extra deaths associated with HRT use.

Lead author Professor Valerie Beral, Director of the Cancer Research UK Epidemiology Unit, says: "We estimate that over the past decade use of HRT by UK women aged 50-64 has resulted in an extra 20,000 breast cancers, oestrogen-progestagen therapy accounting for 15,000 of these.

"Combined oestrogen-progestagen HRT is usually prescribed for women who still have a uterus, to avoid the increased risk of cancer of the uterus caused by oestrogen-only therapy.

"Since our results show a substantially greater increase in breast cancer with combined HRT, women need to weigh the increased risk of breast cancer caused by the addition of progestagen against the lowered risk of uterine cancer.

Comparing the risks is by no means simple, and women may well want to discuss options with their doctor."

Julietta Patnick, Director of the NHS Cancer Screening Programmes, says: "Women often ask us about the factors that can influence the risk of developing breast cancer, and we worked with the study team to initiate the Million Women Study to help find answers to such questions.

"Through NHS Breast Screening Units, over a million women were recruited to the Million Women Study, making it the largest ever study on the factors that can influence women's risk of breast cancer.

"I would like to thank the 66 Breast Screening Units and the women who took part in this study. I hope that the results will help provide women with the information they need to make an informed choice about use of HRT."

Dr John Toy, Medical Director of Cancer Research UK, says: "Previous reports have indicated that breast cancer risk increases in women taking HRT and this vast new study, the largest ever conducted, has allowed accurate assessment of the size of the effect.

"On a national scale, with so many women taking HRT, the number of extra cases of breast cancer has been quite large, but the increased risk does start to fall on stopping treatment.

"It would be sensible for a woman to take HRT for only as long as it is necessary to deal with her medical problems as advised by her doctor. A woman wanting to take HRT for a long time would be extremely wise first to consider carefully the findings of this large study and other relevant research."