Published online 8 August 2003 | Nature | doi:10.1038/news030804-13


Long-term hormone replacement linked to breast cancer

One million menopausal women reveal risks of therapy.

HRT alleviates hot flushes, sweating and mood swings and reduces the risk of bone wastingHRT alleviates hot flushes, sweating and mood swings and reduces the risk of bone wasting© DigitalVision

Women taking combination hormone-replacement therapy (HRT) may be twice as likely to develop breast cancer. So concludes a study involving a million British women, the largest ever to probe the suspected link1.

In response to the findings, Britain's drug regulator today changed its HRT advice. Doctors are now required to appraise patients of the risks of prolonged therapy and to discuss the relative costs and benefits with them annually.

Around 1.5 million British women take HRT to alleviate menopause-associated hot flushes, sweating and mood swings, and to reduce the risk of bone wasting. Around half take a combination of the hormones oestrogen and progestogen. Progestogen cuts the risk of uterine cancer in post-menopausal women who have not had a hysterectomy.

Over the past decade, some 20,000 extra cases of breast cancer in British women aged between 50 and 64 are attributable to HRT, the new study finds - three-quarters of those are linked to combination therapy. This risk is only associated with HRT taken for ten years or more - cancer incidence falls appreciably the less time a woman spends undergoing the therapy.

"Women need to weigh the increased risk of breast cancer against the lowered risk of uterine cancer," says study leader Valerie Beral of Cancer Research UK.

Oestrogen-only HRT carries a risk too: a 30% increase in breast cancer for women on oestrogen-only therapy, compared with 100% for those taking the combination. The study is the first to separate the effects of the two regimens.

"We're not talking about a medical emergency here," says John Toy, also of Cancer Research UK. If anything, the new research gives doctors the data they need to provide more sound advice.

The survey shows, for example, that breast-cancer risk due to HRT occurs earlier than previously thought - after only two to three years of therapy. The risk after just one year is negligible, and five years after stopping HRT the risk returns to baseline.

The study also reveals that the risks associated with tablets, patches and implants are the same. The relative breast-cancer risk of each had been disputed in previous studies.

"Now we can actually give women an evidence-based answer," says Julietta Patnick, director of cancer screening with the UK National Health Service.

Deciding what answers to give will be problematic. Balancing HRT's quality-of-life benefits with the reduced risk of uterine cancer and increased risk of breast cancer is complex. "It's a dilemma and there is definitely no simple answer," says Beral.

Doctors' strategies may also be influenced by results from an ongoing US study, published yesterday2. The survey highlights a slight but significant increase in the risk of heart disease during the first year of combined HRT. Initial research suggested that HRT might protect women from heart disease.

New guidelines released today by Britain's Committee on Safety of Medicines urge each woman's case to be treated individually. The committee does not advise against therapy for a year or less, says spokesperson Mary Armitage. "Here the benefits clearly outweigh the risks," she says. 

  • References

    1. Beral, V. and the Million Women Study collaborators. Breast cancer and hormone replacement therapy in the Million Women Study. Lancet, 362, 419 - 427, (2003).  | Article | ISI | ChemPort |
    2. Hodis, H. N. et al. Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. New England Journal of Medicine, 349, 535 - 545, (2003).  | Article | ISI |