Scientists at Cancer Research UK say they now have conclusive proof that tamoxifen can prevent breast cancer in healthy high-risk women.
An international team led by Professor Jack Cuzick, a world-renowned scientist and senior researcher at the charity, conducted an extensive review of the drug’s track record in prevention trials.
The findings, published in the Lancet1, show that drug reduced the incidence of breast cancer by 38 per cent in healthy women with a high chance of developing the disease.
Researchers say the next challenge is to minimise the side-effects of tamoxifen so that it can fulfil its potential as a frontline preventative drug.
Prof Cuzick, of the Cancer Research UK Epidemiology, Mathematics and Statistics Group in London says: “In our analysis we combined all the available evidence from studies using tamoxifen for breast cancer prevention – collectively involving over 40,000 women – and it is clear to us now that the drug can reduce the chance of high-risk women developing the disease.”
The team, involving scientists from Australia, Italy and the UK, combined and re-analysed the results of 14 trials including data on breast cancer prevention.
They examined results from four of them, involving 28,000 women that tested the role of tamoxifen as a preventive treatment. They also looked at one, involving 7,700 women, which tested the performance of the drug raloxifene. The trials compared the performance of both with a placebo.
Nine trials involved 15,000 women who had a tumour removed from one breast and were treated with tamoxifen to prevent cancer returning.
Researchers calculated the reduction in breast cancer incidence and found it fell substantially in the tamoxifen trials and in the raloxifene trial it dropped by 64 per cent.
In the trials using tamoxifen after an initial tumour had been removed scientists found that the number of new cancers in the opposite breast dropped by 46 per cent.
Tamoxifen was only able to prevent breast cancers that carry receptors for the hormone oestrogen. There was no reduction in incidence for women with oestrogen receptor negative breast tumours.
Researchers also calculated the risk of side-effects from the treatments and found that women on all of the trials taking tamoxifen or raloxifene had an increased risk of developing blood-clotting disorders – with a more than two-fold increased risk seen for each drug.
The study also found that women taking tamoxifen had a two-fold increased risk of developing endometrial cancer – a much less common cancer than breast cancer occurring in the lining of the womb. But the trial of raloxifene showed no increased risk of the disease.
Prof Cuzick says: “The evidence to date clearly shows that tamoxifen can reduce the risk of breast cancers stimulated by the hormone oestrogen. However, it is crucial that we follow all the trials to their conclusions and find ways to reduce the side-effects of tamoxifen before we can recommend that high-risk women take the drug to prevent breast cancer.”
“It may be possible to reduce side-effects of tamoxifen by using a lower dose or adding low dose aspirin. Carefully selecting women to exclude those already at risk of blood clotting disorders or endometrial cancer may also be a way of making the use of tamoxifen more viable.”
He adds: “The early data on raloxifene looks very promising – the trial shows that the drug can reduce the risk of breast by 64 per cent and cause fewer side-effects than tamoxifen. We will be awaiting the results of its direct comparison with tamoxifen in the American STAR trial with great interest.”
“The future challenges for prevention research are to find ways to reduce the side effects of tamoxifen and investigate new agents such as aromatase inhibitors. One such drug, anastrozole was found to prevent 70 per cent of new tumours in the opposite breast when used as treatment for postmenopausal women with breast cancer.”
Sir Paul Nurse, Chief Executive of Cancer Research UK says: “It looks clear to us now that tamoxifen has a important role in preventing breast cancer. But it is essential that we continue to monitor tamoxifen’s long-term performance in prevention trials and to identify those women in which the benefits of drug will outweigh the risks.”
He adds: “The results from the raloxifene trial are very interesting but we need further evidence on this drug’s and anastrozole’s effectiveness in breast cancer prevention.”
- Lancet361 9354 pp.296-300
Breast cancer affects around 40,000 women in the UK each year.
Endometrial cancer affects around 5,000 women in the UK each year.
Almost two-thirds of tumours from pre-menopausal women and three-quarters of tumours from post-menopausal women contain detectable oestrogen receptors, which means their growth is stimulated by the presence of oestrogen.
Tamoxifen has only been effective as a treatment for oestrogen receptor positive breast tumours.
Raloxifene is a drug used for the prevention and treatment of osteoporosis in postmenopausal women.
Aromatase inhibitors are a new class of drug that can virtually eliminate oestrogen in postmenopausal women by blocking its production.
STAR – Study of Tamoxifen and Raloxifene is recruiting in the United States, Puerto Rico and Canada. The trial will include 22,000 postmenopausal women at increased risk of breast cancer to determine whether raloxifene is as effective in reducing the chance of developing breast cancer as tamoxifen.