Effects of aspirin on the progression of cancer

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Published: 1 Nov 2012
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Prof Peter Rothwell – Oxford University, UK

Two main finding from a number of long-term trials found that aspirin effects cancer incidence in the very early stages of its development. As a result, these positive effects are not seen for five to ten years, but the overall effect is a reduction in incidence and morbidity, predominantly in gastro and colorectal cancer.

 

Short term affects of aspirin are that patients who develop cancer are less likely to have blood born metastases.

 

Prof Rothwell also discusses the lack of information on breast and gynecological cancers.

There are two main findings really, one is that there’s an effect of aspirin, a beneficial effect of aspirin, on cancer incidence. This appears to be an effect of aspirin on the very early development of cancers and so as a consequence of that you don’t actually see the effect for five, really ten, years for most cancers. Aspirin starts to work immediately but then the cancer takes five years to grow or not to grow. Then after about ten years you get suddenly a reduction in mortality and incidence of some cancers. We and others have shown this fairly clearly now for colon cancer, particularly proximal colon cancer, but also for other GI cancers, most notably oesophageal cancer where there seems to be about a 60-70% reduction in incidence and mortality after about seven, eight, nine years.

So there’s the long term effect on incidence but one of the other things we found unexpectedly was that there was also a shorter term effect on mortality in people who had been randomised in these trials of aspirin in prevention of vascular disease. There were fewer deaths due to cancer after three, four, five years in those trials. That would be too quick to be due to an effect on incidence of cancer, on the development of cancers, so it seemed to us that must have been an effect on the growth or the spread of cancers. So we then looked in detail at those cancer outcomes that occurred in these trials by going back to their records and found that what was happening was that those patients who developed cancers in the aspirin group were much less likely to have metastasis at presentation and much less likely to develop metastasis later. When I say metastasis, that’s really blood-borne metastasis, so distant metastasis to brain, lung, liver or wherever. It seems that there are these two independent effects which may have different mechanisms, may have different dose responses but aspirin seems to be responsible for both of them – the reduction in incidence of some cancers and the reduction in risk of metastasis of cancers if they’re already there.

Do you feel there is a lack of data on female trials with aspirin?

Yes, one of the problems is we looked at mainly trials done some years ago in prevention of vascular events which, because the risk of vascular events is so much higher in men than women, or was in those days, they were done predominantly in men. So it’s only in the more recent trials that there are data on women. We did look at males versus females in some of our recent papers and the effects, certainly on metastasis and on incidence, seem to be similar in men and women. So there’s no reason to suspect that where there is an effect on a particular cancer it’s only in men. I think the big question in women is is there any effect of aspirin on breast cancer and on gynae cancers because together they account for about 75% of cancers in women. So it’s quite possible that aspirin won’t have an effect on overall cancer incidence in women because it might not affect the main cancers in women.

Are there any ongoing trials?

Yes. All the trials we looked at were trials of daily aspirin but there is a big American trial of alternate day aspirin, the Women’s Health Study, which is about to report results on long-term follow-up out to about 17 or 18 years. So that will give reliable data on the effect of alternate day aspirin and if one assumes that that will be the same as daily aspirin then that would be helpful certainly.

Could you briefly discuss novel collaboration?

Yes, one of the things we’re trying to do is to continue to add to the collection of individual patient data on the effects of aspirin on cancer but also, in fact, on the effects of aspirin on a whole host of other non-vascular complications or diseases. One of the striking effects of aspirin in the trials in vascular disease is in fact that it doesn’t reduce vascular death but there is a very consistent reduction in non-vascular death. Some of that is due to effects on cancer but there are other very interesting signals in relation to effects on infection and certain neurological diseases. So we’re continuing to collate all the individual patient data from previous and from ongoing trials to try and have enough numbers to define some of those effects more reliably.

What do you feel are the risks and benefits of taking aspirin daily?

It’s tipping that way. As you know the guidelines, particularly in the US, before any data on cancer already suggested that the benefits do outweigh the risks. The question is is the overall benefit worth having? It’s a small benefit but when you add the cancer benefit on top of that clearly it pushes it more in that direction. But I think it comes down to individuals to decide for themselves; the effects of stopping smoking would be a lot bigger than taking aspirin, the effects of regular exercise and a good diet would probably be equivalent. So it’s something to consider alongside those things but it certainly wouldn’t be an alternative to stopping smoking, for example.