Researchers have discovered some of the secrets of how the drug tamoxifen prevents breast cancer in women at high risk.

The breakthrough could pave the way for the development of a new generation of more effective disease-preventing medicines without side effects.

Tamoxifen works by blocking the breast cancer-causing effect of the sex hormone oestrogen.

However, it is also believed to increase the risk of contracting cancer of the uterus.

US scientists, from Chicago and San Francisco, believe the discovery of the precise molecular mechanism behind taxomifen could enable the development of drugs with enhanced efficacy and reduced side effects.

Writing in the scientific journal Cell, Professor Geoffrey Greene, from the University of Chicago, said: "The goal is to figure out how to make drugs that retain the benefits of oestrogen for brain, bone and heart and also have the benefits of oestrogen blockers for the breast and uterus."

His colleague Andrew Shiau, from the University of California at San Francisco, said: "This research sets the stage for the intentional design of drugs with precise and selective action."

Oestrogen has many health benefits. It delays the build-up of artery-clogging plaque, prevents bone loss leading to osteoporosis, and may even postpone the onset of Alzheimer's disease.

Cancer risk

Professor Geoffrey Greene uncovered the molecular pathway

These benefits disappear at menopause, when women stop making significant amounts of oestrogen.

Although taking replacement oestrogen can restore these benefits, and prevent the hot flushes of menopause, continued exposure to this hormone increases a woman's risk of breast or uterine cancer.

Tamoxifen is one of a group of drugs known as selective oestrogen receptor modulators (SERMs).

These drugs function like oestrogen in some tissues, but block oestrogen's effects in others.

The problem with tamoxifen is that while it may block the potentially harmful action of oestrogen in the breast, it retains oestrogen's tendency to promote cancer of the uterus.

Another SERM, raloxifene, appears to have similar benefits with less risk of uterine cancer. The two will be compared head-to-head in a large clinical trial beginning next year.

Oestrogen works by binding to a specific receptor, found only in the cells of certain types of tissue.

Once oestrogen has "docked", the receptor is activated to respond to proteins that either promote or repress growth in the tissue. Uncontrolled growth can lead to cancer.

The new research has found that tamoxifen alters the normal shape of the receptor and prevents it from interacting with those proteins.