Update on Aspirin and Cancer Prevention

Jack Cuzick, PhD

We were very interested in the role of aspirin in preventing cancer. We did a consensus statement^[1] about 2 years ago in which we said the data looked very promising, but what was needed was longer follow-up of the ongoing trials. Much of that has now taken place, and some new results have come out, so the results look even more promising.

What is particularly clear is that the effect of aspirin on prevention is a long-term effect and that not very much happens in the 5 years after you start taking aspirin. The preventive effects are really quite long-term; that is very important in terms of how it should be used, if you are going to need to start 5 years before there is going to be any benefit.

There have been 2 recent papers. One was on patients with Lynch syndrome, which puts them at high risk for colorectal and a few other cancers. That was a trial of both starch and aspirin, and the initial results^[2] when they were published a few years ago were actually negative for both of these. There was no effect at all, and now with additional follow-up,^[3] we have seen what was seen in many other studies or was emerging in many other studies: that the effects take a long time to kick in, so now there is a substantial reduction in cancer, particularly colorectal cancer, but some additional cancers as well.

This was a high-dose trial, so again, it doesn't actually address directly the question of whether low-dose aspirin is appropriate. The dose that was tested was 600 mg/day (2 standard aspirin tablets per day), so there were many questions about how best to use aspirin both in the general population and in patients at high risk. The dose is one question.

There was another recent paper from Professor Rothwell and colleagues^[4] looking at a whole range of cancers in the randomized trials, and again, the same feature showed up -- that the effect is quite long-term. Not very much happened in the first 5 years of treatment, but after that, preventive effects emerge for a number of cancers. The most striking were, again, colorectal cancer, esophageal cancer, and to some extent stomach cancer. So it looks like all of the gastrointestinal cancers might be quite substantially affected, with maybe as much as a one-third reduction with long-term aspirin use.

There also was emerging evidence for a few other cancers, notably breast cancer, ovarian cancer, lung cancer, and prostate cancer. The evidence is less clear and less striking, but overall the deaths from cancer in these studies were reduced by 20%, so there is something going on above and beyond just what was seen in the colon cancer study.

There are many possible mechanisms. It could be as simple as the fact that aspirin reduces inflammation, and inflammation is associated with more rapid cell turnover. The more times a cell divides, the greater the chance for an error that could lead to a mutation leading to cancer. It could be as simple as that. There are many more complicated explanations as well. There is plenty of room for research, both at the mechanistic level in terms of trying to understand what is going on, and more applied research, in trying to figure out what is the best way that we can live with low-dose aspirin for cancer prevention. The data from the Rothwell paper suggest that the low dose may be as effective as the higher dose, but we probably need more evidence to be quite certain about that.

The other major issue is at what age to start and stop taking aspirin, and that is very much a balance between the benefits in terms of cancer and heart disease and the risks in terms of gastrointestinal bleeding. There is emerging evidence that bleeding effects are only serious in individuals over the age of 70 years and that typically in younger people, they aren't so serious and they tend to disappear after stopping treatment, without any serious problems. That needs to be looked at more, but it does suggest that one should maybe be thinking about starting aspirin around age 50-55 years, and maybe taking it for 5-10 years and then trying to finish taking it before you get to age 65-70 years, when the side effects are potentially more serious. That is very much an area for research. We don't really have clear answers, but those are suggestions.

The other major area for research is trying to identify subpopulations at increased risk for gastric bleeding and trying to find ways to either avoid aspirin in that group or address the issues. One of the things that is striking and quite simple is that there is substantial evidence that the bleeding and the ulcers caused by aspirin are a particular problem in people who have Helicobacter pylori infection, so maybe a simple thing like testing and eradicating that organism before you start aspirin therapy might go a long way toward reducing those side effects