We discuss whether chemoprevention has lived up to its promise.
"If you don't prevent people from dying, then how valuable is that?" - Professor Mike Dixon questioning the benefit of chemoprevention.
This week at the Annual Miami Breast Cancer Conference, Professor Mike Dixon questioned the value of tamoxifen as a breast cancer chemopreventative – that is taking the drug before breast cancer develops to reduce the risk of it occurring.
In June 2013, the National Institute for Health and Care Excellence (NICE) recommended for the first time that two drugs, tamoxifen and raloxifene, should be made available on the NHS in England and Wales for women at increased risk of developing breast cancer. This was widely heralded as a game-changer by Breakthrough and other charities. Two years later and questions are starting to be asked – has chemoprevention lived up to its promise?
A new use for old drugs
There is clear evidence that tamoxifen, long used as a breast cancer treatment, can also reduce the risk of a breast cancer developing in the first place. Studies such as IBIS-1 have shown that taking tamoxifen for five years can reduce the risk of breast cancer developing by around one third – giving women at increased risk of breast cancer another way to help reduce their risk of the disease.
However, Professor Dixon’s point is that the long term benefit isn’t so clear. More recent analysis of the IBIS-1 study reveals that even though a preventative effect can still be seen after 20 years, there doesn’t appear to be any difference in the number of deaths related to breast cancer.
Confusingly, there were slightly more deaths amongst women who had tamoxifen as a preventative, although there was a reduction in the number of breast cancer cases. This is complex, and suggests that women who take tamoxifen to prevent breast cancer are just as likely to die from breast cancer as those who don’t, but they are less likely to develop breast cancer in the first place. It may be that for those women who do still develop breast cancer, it is harder to treat. For example, women with a faulty BRCA1 gene tend to develop ER-negative breast cancers, for which tamoxifen and raloxifene do not appear to be effective against as a preventative.
What this unfortunately shows is that not all breast cancers can be prevented and, given that tamoxifen has some significant side effects, there are more complex considerations that need to be made when offering chemoprevention to women.
Considering side effects
Although the option of chemoprevention is now available, implementation of the NICE guidelines is complicated. It’s not yet clear at what age it would be best to suggest women take chemoprevention for the greatest long-term benefit and there are risks to prescribing a drug with significant side effects to healthy women who may not go on to develop breast cancer. Recommending chemoprevention at the moment needs to be considered on a careful patient-by-patient basis.
Another major issue is that GPs may be reluctant to prescribe chemoprevention, and then to monitor patients who are taking it. Anecdotally, we have heard that the fact that tamoxifen is not licensed for use as a preventative drug is a major barrier – even with NICE’s recommendation.
Weighing up the risk
Perhaps a bigger issue is that many of the healthcare professionals we have spoken to feel that the number of women choosing to take up chemoprevention as a risk-reducing option is likely to be low. It’s possible that women at moderate risk, for whom surgery is not recommended, don’t feel that the level of absolute risk reduction justifies the side effects of taking tamoxifen or raloxifene.
A woman with an 18% (two in 11) lifetime risk of developing breast cancer could expect her risk to be reduced to around 12% (one in eight) with a chemopreventative – an absolute reduction of 6%. Similarly, it was felt that women at the highest levels of risk may prefer surgery, which gives a much greater risk reduction. Nonetheless, chemoprevention remains a good option for some women, particularly those who may not want to have risk-reducing surgery, or want to delay it.
Breast cancer can be prevented
So although some questions remain over chemoprevention, what is clear is that some breast cancers are preventable. For some women, this could be by lifestyle changes, for others drugs could provide additional benefit, and for the groups at highest risk, surgery remains a good option.
Breast cancer incidence is on the increase and we must act now to reverse this trend. We will continue to work to ensure more women at risk of breast cancer are identified, so they have every chance of taking action to prevent the disease. We need to do more not just to ensure effective prevention methods are developed, but also that they can be made available on the NHS so the women who will benefit the most can do so.