In the US, tamoxifen was approved for preventing breast cancer in women who had never had the disease in 1998, after research published the same year found that in women with a family history of breast cancer, the drug reduced the risk of getting the disease by almost half. Another drug called raloxifene, designed to protect bone density after the menopause, was also licensed for breast cancer prevention after research involving 19,000 menopausal women found it halved the incidence of breast cancer.
But despite the promise shown by these drugs, neither has been widely used to prevent breast cancer. This is mainly because both carry a small risk of life-threatening blood clots (although the risk with raloxifene is smaller than tamoxifen) and other serious side effects. Tamoxifen can also cause endometrial cancer (of the lining of the womb) in rare cases.
The good news about anastrozole and exemestane, the drugs undergoing more recent trials, is that they appear to have far fewer serious risks. Still, these powerful drugs can have unpleasant side effects, such as making hot flushes worse. Prof Goss, a director of breast cancer research at Massachusetts General Hospital, also concedes it is "theoretically possible" that they could weaken women's bones, if taken for a lengthy period. Both drugs belong to a class of drugs called aromatase inhibitors which halt the production of oestrogen, rather than just blocking its uptake by cancer cells; as such they are only suitable for use in women after the menopause.
Experts concede that while the new drugs show promise, no medication is free of risk. The field of chemoprevention is fraught with dilemmas: how do you weigh up the risk of side effects in healthy women against the potential benefits of the drug?
"If [exemestane] was free of side effects, we would say put it in the water [supply]," says Prof Goss. As it is, drugs for breast cancer prevention are being aimed at those for whom the benefits probably outweigh the potential harm – women at high risk of getting the disease. "High risk" is usually defined as those whose mothers or sisters had breast cancer (or ovarian cancer) by the age of 50.
Another challenge for proponents of chemoprevention is how to be accepted by patients and doctors – a tricky task when there are no immediate, tangible benefits, only the potential to reduce risk. "Cardiologists have been able to sell the concept of prevention to patients, by pointing to something that's working, like 'Your cholesterol is coming down,'" explains Prof Goss. "We haven't been able to do that with breast cancer."
In addition, in the UK, one major problem has been the absence of any regulatory approval of drugs for breast cancer prevention. The reason is down to money, according to Prof Cuzick. With the lucrative patents for tamoxifen and raloxifene now having lapsed, generic versions of these drugs can be made very cheaply. Since this effectively reduces potential profits, there is little incentive for drug companies to go through the expensive process of applying for a new marketing licence from the EU or UK regulatory bodies.
"It's a real Catch-22," says Prof Cuzick. "What would be sensible is if academic institutions, like Cancer Research UK and the Medical Research Council, came together to present the research data and get chemopreventive drugs licensed as generics," he adds. "So far there's been no progress on this suggestion – but it would be a good solution."
'I went on the trial because I saw how devastating cancer was for my mum’
Sue Holloway, who lost her mother Pauline to breast cancer while a teenager, is convinced about the potential benefits of taking drugs to prevent this devastating disease.
''For 15 years, my mother battled very hard against breast cancer,” says Sue, a pharmacy assistant from Langthorpe in Yorkshire. “Throughout my childhood I remember her being ill. I was 17 and she was 44 when she died.’’
Sue became a mother at 28, when she adopted Joanna. The last thing she wanted was for history to repeat itself. So when the opportunity came to be part of a trial looking at the effectiveness of the drug anastrozole in preventing breast cancer among healthy women, she leapt at it. ''I went on the trial because I saw how devastating breast cancer was for my mum,’’ says Sue.
She took anastrozole for five years, between 2003 and 2008, as one of the first recruits for the Cancer Research UK-sponsored IBIS-II trial, which is comparing anastrozole against a placebo in post-menopausal women with a family history of breast cancer. Sue will never know if she was taking the active drug or the dummy (like most trials, this one is “blinded” to both patients and researchers to avoid bias creeping in).
''But I suspected I was taking anastrozole because I got side effects,” she said. “My hot flushes got worse, I had stiff joints and my skin became very dry.’’
Sue mother’s cousin and aunt also suffered from breast cancer. Sue has not developed the disease, although whether the drug reduced her risk she will never know. But as results from more than 6,000 women trickle in, scientists hope to be able to tell by 2013 how effective anastrozole is in preventing breast cancer in high-risk women. Should the results prove positive, Sue wants to see it licensed as soon as possible. ''Women need to realise the risks and the side effects of the drug, but to me if your risk of breast cancer is high, it’s worth it.’’
The IBIS-II trial is recruiting women at high risk of breast cancer. Visit www.ibis-trials.org for details