BACR & ECMC: Therapeutic interventions for cancer prevention
The future of cancer prevention
Prof Jack Cuzick - Wolfson Institute of Prevention Medicine, London, United Kingdom
I was asked at this meeting to try to give my thoughts about where cancer prevention is going in the next ten years which is a daunting challenge because it’s a very widespread field from basic science right up to very large clinical trials. So it was only my own personal perspective and I identified five areas which I thought we should really focus on. One is the repurposing of currently available drugs; I think this is an area where we’ve had our current successes. The two great successes for cancer prevention are really anti-oestrogen treatment for breast cancer and there we’ve got the great advantage that women have two breasts, they get treated with adjuvant treatment for one breast and we can use the other breast as an indicator of what’s going to happen in the preventive setting. That’s been a very good predictor which has been clearly borne out with both tamoxifen and now the aromatase inhibitors.
The other great success has been aspirin, where again we’ve been able to latch on to a lot of trials in which aspirin was looked at very thoroughly for cardiovascular disease and we’ve been able to go back and capture the cancer data to get its unsuspected late impact on a range of cancers and that’s very, very exciting. The challenge is to do that for a range of other drugs, there are a number that are being looked at now. Metformin, of course, is a very interesting one; the bisphosphonates look quite interesting for cancer, particularly breast cancer, and there’s a whole range of other things.
The big challenge is to properly evaluate agents that have not been involved in treatment of other diseases where we have mostly just epidemiologic data. The dietary factors are a good example of that and we’ve gotten burnt in the past, for example beta carotene, selenium, vitamin E were all suggested in epidemiologic studies to be good cancer preventive agents and, in fact, when the large randomised trials were done they’ve all been negative. So I think we have a real challenge there. These large trials are hugely expensive and because of the negative results in the previous dietary ones there’s not a great appetite, if you take the word, to look at dietary factors in randomised ways. But there are a range of things, there’s curcumin, there’s the omega fatty acids, a whole range of things that could be looked at, but how we’re going to get good evidence is a real challenge.
One of the areas where I think we might be able to make progress is to try to look at the impact of these agents on precursor lesions, not go to the general population in the first case but to go to individuals that have early lesions that maybe are not being actively treated or are being treated in a very minimal way. So ductal carcinoma, DCIS, in breast cancer, advanced adenomas in colorectal cancer, to some extent CIN in cervix cancer although that’s usually pretty fully treated and then lastly but maybe most importantly are early prostate lesions. There they’re not precursors but they’re early invasive cancers, the Gleason 6s and Gleason 3 4s which in many cases are managed by active surveillance. This is a great population to see if preventive agents will work because first of all you’ve got a very motivated group, they’ve had a cancer, secondly they’re not getting very much except for repeat testing every year so they’re quite willing to consider agents. We’re currently just about to start a trial called PROVENT in prostate cancer to look at aspirin and vitamin D but I think there are a range of other things that could be looked at in this patient population.
The last area I want to say something about is I think that we have to recognise that we’ve got to do a better job in advocacy for cancer prevention. Cardiologists figured this out decades ago and have managed to label things like hypertension or high cholesterol levels as diseases which need treatment and, as a consequence, preventive therapy is very common for cardiovascular disease. We need to find some way to do similar things in cancer. We don’t really have good biomarkers that we can study to see whether or not a treatment is actually working as cholesterol levels are for cardiovascular disease but I think we could begin to do that. We have breast density for breast cancer; if you can show an agent reduces breast density that’s a strong indicator that it’s going to be effective. That’s good for a number of things – first of all it will shorten trials if we can use that and, secondly, individuals that see a beneficial impact of a preventive therapy are going to be more willing to continue with it.
So those are essentially some of my prospects for the future. I think it’s a daunting area, there’s things that are happening in many, many directions. So just my own perspective on that. Thank you.