You underscored this cancer prevention fact earlier. A person needs to take Aspirin for at least five years, in order to see dramatic effects of cancer prevention. Correct! Dr. Anton Titov, MD. How many years do you have to take Aspirin for prevention of cancer? Dr. Anton Titov, MD. Why is there such a long lag period to see cancer prevention effects of Aspirin? Dr. Jack Cuzick, PhD. I think it's uncertain why it is such a long period. The most likely explanation is that cancer is not just a disease, it's a multi-stage process and there are early and late stages. Probably, this is true. Aspirin is working on some of the early stages of cancer formation. These early stages of cancer formation will take a long time to develop into cancer. How long you should take Aspirin is not known with certainty. It's clear you have to use Aspirin for at least 5 years. Whether 10 years is better than 5 years of using aspirin is an open question. We'd like to do a clinical trial of duration of taking Aspirin for best cancer prevention. Dr. Anton Titov, MD. Side effects of Aspirin are essentially gastrointestinal bleeding. That really only occurs while you're taking Aspirin. So perhaps you can get the benefit with 5 years of using aspirin for cancer prevention. Dr. Jack Cuzick, PhD. Then you don't need to continue taking aspirin. Then, of course, a major side effect of aspirin use would disappear. That would be better for your overall benefit vs. harm ratio. But perhaps there is not this long carryover effect of cancer prevention after you stop using aspirin. Whether or not 5 years of Aspirin will give you 20 years of cancer protection, is not known. We saw a long effect of cancer prevention with tamoxifen in breast cancer. Dr. Jack Cuzick, PhD. Exactly! Sometimes that's true for colorectal cancer. We don't know the answer yet. We do not know that aspirin use for 5 years is enough for prevention of cancer. But you may need to continue taking aspirin for longer than 5 years. Then we need to look at the time when you should stop. We know that gastrointestinal bleeding risk increases with age. Side effects of aspirin associated stomach bleeding are also more important at older ages. So there is real benefit in being able to stop aspirin. But the benefits of cancer prevention by aspirin may last longer. Then we have to look very carefully what the right age is for stopping Aspirin. Dr. Anton Titov, MD. One of Aspirin's major side effects is gastrointestinal bleeding. It is also linked to Helicobacter pylori infection. Perhaps people should be tested for Helicobacter pylori infection. Absolutely! We we would like to run a very large clinical trial. We will evaluate three of these unknown ideas about how is best to use Aspirin for cancer prevention. First, about 20% of the 60-year-old population have Helicobacter pylori in stomach. But they are completely asymptomatic. They don't know it. H. pylori infection can be easily tested for. It can be eradicated with antibiotics. That would have a major impact on reducing the amount of bleeding you get with Aspirin. It will probably be about a third [30%] less stomach bleeding when you completely eradicate Helicobacter pylori infection. Dr. Jack Cuzick, PhD. So that's probably worth doing. But again, we'd like to do a clinical trial to demonstrate the length of time for use of aspirin in cancer prevention. The second question is this. Is low-dose Aspirin as good as standard dose Aspirin? The indirect evidence suggests that it is true. Many of clinical trials for cardiovascular disease used the low-dose aspirin. Dose was between 75 and 100 mg. The benefits of aspirin have been as big. They were maybe a little bigger even with low does than with the standard dose of aspirin. So there's indirect evidence that low-dose aspirin is best for cancer prevention. But there's no direct comparisons. There are no clinical trials that randomized individuals to take either a low-dose Aspirin or standard-dose Aspirin. The third question is this. You have already alluded to it. Dr. Anton Titov, MD. How long should you take Aspirin for cancer prevention effect? Is 5 years enough or should you carry on longer? All of those hypotheses can be tested in one large clinical trial. Dr. Jack Cuzick, PhD. You can randomize people to each of those three arms of clinical trial. you can get a very clear answer on how long to take aspirin for maximum cancer prevention. There is a large importance of Aspirin for cancer prevention. The whole population potentially could be taking Aspirin for prevention of cancer. It would seem wise to invest money in doing a large clinical trial to get the clearest answer. But Aspirin is a generic medication. Bayer's patent on Aspirin expired in 1930s. Aspirin is a cheap and widely available medication. At the same time, large clinical trials are very expensive. So the pharmaceutical companies might not have incentive to run them on medication with expired patent. Dr. Jack Cuzick, PhD. I think that's the real challenge. If Aspirin were expensive, you can be certain that the pharmaceutical industry would have promoted and run these clinical trials by now. Because there would be profit to make from use of aspirin for cancer prevention. Not that many very expensive medications have 30% effect on reducing cancer risks. Dr. Anton Titov, MD. But you have a generic cheap medication that has a potentially large therapeutic effect. So we can't expect the pharmaceutical industry to subsidize these clinical trials. This is an area where I think health services and governments have a major role to play. They will get the benefit in terms of reduced cancer. They will have to treat fewer number of patients with cancer. I think it's the government’s responsibility to be conducting these large clinical trials of aspirin use in cancer prevention. They have to determine how is best to go forward with Aspirin in cancer prevention.