Aspirin in the 21st century
Aspirin in the primary prevention of cancer
Dr Andrew Chan – Harvard Medical School, Boston, USA
What is the rationale for using aspirin for the prevention of cancer?
There is now very considerable data which really supports an association between aspirin use and a lower risk of cancer, particularly of the colon. There have been a large number of cohort studies and case controlled studies that have shown that people that take aspirin have a lower incidence of cancer. But now there are quite convincing data that have emerged from randomised controlled trials that show that people that have been randomised to aspirin also have a lower incidence of colorectal cancer. Some of those studies have also showed that there might be also significant reductions in the risks of other types of cancer as well. So I think there’s quite a lot of interesting evidence now that really supports the anti-cancer effects of aspirin.
What evidence specifically favours using aspirin for cancer prevention? What is new?
I think that, as I mentioned, there is randomised controlled trial evidence which is quite convincing, particularly in colorectal. That has really been the big news in the last few years that really has lent a lot of substantial support for its efficacy. The newer evidence now also with other cancer is also quite exciting. What has also been very important in the field is the idea that we’re learning much more about the mechanism of action which is important for a couple of reasons. One, it supports the underlying biology in that we really are seeing causal associations between aspirin use and lower cancer risk but also some of those mechanistic studies have provided some insight into the potential that we can develop biomarkers that could help to predict individuals that may stand to preferentially benefit from aspirin use. Some of those biomarkers include a better understanding of the genetics of colon cancer and the idea that maybe there are particular subsets of the population that are defined by genetic risk that also might stand to benefit more from aspirin use.
What has been some of your research in this area?
We’ve had a multipronged approach. On the one hand we’ve been very interested in understanding the public health ramifications of aspirin use so we’ve been looking very carefully at the associations of aspirin with cancer incidence in very large, unselected populations to really understand what the potential population benefit might be of aspirin use across a broad spectrum of individuals. But we’re also very interested, again, in understanding in a human population what are the potential mechanisms of action because a lot of experimental studies have been done but we often realise that what’s found in experiments on animals isn’t necessarily what’s going on in humans. So we’ve been very carefully looking within human populations to understand what is aspirin doing biologically that could be important. Some of the findings from those studies have led to the idea that we could define specific subsets of the population and define by their genetic risk factors or biochemical risk factors or even their tumour markers that could influence who we might decide to treat with aspirin therapy because those subsets may be more likely to benefit.
Can you tell us about your research recently presented at the AACR meeting?
We wanted to understand in a large unselected population what is the effect of aspirin in terms of multiple cancers. If we take a healthy group of individuals and follow them over the long term, 20-30 years, and really track their use of aspirin over that time period, do we actually see meaningful differences in cancer incidence according to whether people used aspirin or did not. We did find that overall there is this important impact on overall cancer such that there is a lower risk of developing any type of cancer over time but much of that reduction in cancer risk seems to be focussed on reduction in the risk of gastrointestinal cancers, mostly of the colorectum but also, importantly, of other types of gastrointestinal cancer like gastro-oesophageal cancer or pancreatic cancer which I think is important because those are cancers that are very difficult to treat and oftentimes fatal at diagnosis. So we’re trying to understand what is the population-wide impact of aspirin use. Also one of the results of that study which is important is that there seems to be a very large absolute benefit among patients, particularly those that don’t undergo regular colon cancer screening, which perhaps is not surprising but it does suggest that if there are individuals in the population that are not undergoing screening or if there are areas of the world where screening is not generally recommended this could be used as an alternative to screening because in that population you really do potentially see strong absolute risk benefits.
How long do people need to take aspirin for before an effect is seen? Is there a particular dose of aspirin that needs to be used?
Those are all very important questions. I think based on our studies that we have been conducting in population based cohorts but also if you look at the results of clinical trials, there appears to be some sort of delay in the effect of aspirin use. There seems to be some need to probably use it at least five years or so before you start to see substantial reductions in risk of cancers which may not be surprising because cancer tends to be a relatively slow process. So the effect of aspirin on early stages of cancer might not be seen until you’ve used it for quite some time. The dose question is still very important, there are data that support that relatively low doses of aspirin might be effective but not all studies agree, some studies suggest that higher doses may be more effective. So the dose question is still one that still needs to be sorted out. I think there is hope that relatively low doses are effective but it seems pretty consistent that relatively standard doses of aspirin, which include in the US 325mg and in Europe 300mg, that dose seems to be pretty uniformly effective.
From a practical perspective right now, are there certain patients who should be taking aspirin? And those that shouldn’t?
Overall there still lacks any sort of general recommendations of aspirin use for the purposes of cancer prevention, largely because a lot of this data is still new and there’s still a lot of information that needs to be disseminated and a lot of recommendations have to be compiled based upon again weighing risks and benefits of aspirin therapy. In my own clinical practice I think there is definitely a discussion needs to be had between patients and then their providers about whether to use aspirin. In particularly high risk patients I think that discussion could be such that individuals may decide to take aspirin on a regular basis. Some of those high risk populations include individuals that are at high genetic risk for developing colon cancer. There are clinical trial data to support the use of aspirin in the setting of, for example, Lynch Syndrome which is a hereditary colon cancer syndrome where people have a 60-70% chance of developing colon cancer over their lifetime. But there’s also potentially a rationale for people who have strong family histories of cancer or for individuals that are not able to undergo colon cancer screening, either by choice or because there’s a difficulty in them undergoing the procedure, for those individuals there could be potentially a strong rationale for using aspirin in the absence of other alternatives for prevention.
What are your future research plans?
We’re interested again in understanding again the population-wide impact of aspirin therapy. We need to further clarify what is the absolute risk benefit particularly in subsets of the population that are defined by risk factors. Some of those risk factors could be genetic, some of those risk factors may also be based upon lifestyle profiles. So we’re interested in understanding either individuals that are at high risk of developing cancer on the basis of obesity or other risk factors and does aspirin play a special role in such populations. We’re also hoping to really incorporate the effects of aspirin on cancer into analyses which also take into account the effects of aspirin on vascular disease. I think there are already, obviously, very clear compelling reasons for people to take aspirin in the prevention of vascular issues, particularly if they have a history of those problems. So understanding how those things work together in weighing and deciding the weight of the risk benefit profile for an individual are important because we understand, obviously, that heart disease and cancer are really the two leading causes of death in most of the world. So if aspirin can have a meaningful effect on both of those particular diseases and endpoints then for many people the risk benefit could really be tilted in favour of using aspirin.
Do you have a take home message?
I think the take home message is have a conversation with your patients. The data are there to potentially support its use. An understanding of the limitations of the data are necessary and that should be part of the discussion but because our patients are informed and are hearing more and more about the use of aspirin for chronic disease prevention it’s incumbent upon us as physicians to be able to educate them about the potential risks of taking aspirin as well as the potential benefits to help them make an informed decision as opposed to taking aspirin without any monitoring or not taking aspirin because of maybe too much fear of the side effects when potentially they could stand to significantly benefit. So I think in general the lesson is it’s out there, it’s generally safe, there’s generally some really very supportive data for its use in many individuals so having an informed discussion with a patient is really important going forward.
