Could Daily Aspirin Help Prevent Cancer?

Issue 20, 2012

Aspirin, a familiar drug worldwide, was first synthesized in France in the 1850's and commercialized by Bayer in Germany around 1900. It quickly became a standard treatment of colds, fever, and minor pain problems. In the 1970's and 1980's, clinical trials showed that aspirin prevented heart attack and stroke.

All this is old stuff (more or less) - but something new has emerged from a series of papers examining cancer in many of the trials that established these cardiovascular benefits. The new studies suggest that daily aspirin use has the potential to prevent several cancers, and may even improve survival in individuals who do get cancer.

These studies culminate more than three decades of research. In the 1980's, epidemiological studies began to show that individuals who used aspirin regularly had a lower risk of cancer, particularly colon and rectal cancer. There were similar findings for other GI cancers (stomach, esophagus). To gain such effects, continued aspirin use seemed required - once stopped, the cancer risk returned to the previous levels.

These studies also suggested that the "aspirin effect" was far from immediate. In fact, a meaningful cancer preventive effect was not apparent until about 10 or more years after starting the drug.

The epidemiological data are mixed regarding cancers outside the GI tract, such as those in the lung, prostate and breast. But some studies found that individuals who took aspirin long enough had decreased risk of these cancers too.

Findings like these, though very exciting, couldn't prove that aspirin really prevented cancer. For one thing, people who take aspirin regularly differ from those who don’t in ways that are related to cancer risk. Statistical adjustments are used to deal with that, but evidence from randomized studies – real experiments – are needed to be sure that the preventive effects are not due to other characteristics of people taking aspirin.

Randomized trials studying prevention of colorectal adenomas - benign precursors of most colorectal cancers – confirmed the protective effect of aspirin, but the medical community naturally hoped for trials studying cancer itself.

Unfortunately, it would be difficult now to start such a trial. In order to have enough cancers to study, such a trial would have to include tens of thousands of people and last 15 or more years, in order to incorporate the latent period that the epidemiological studies suggest.

So getting long-term follow-up cancer data from the cardiovascular trials was a clever and very welcome development. And what did their data show? As in the epidemiological studies, aspirin reduced the risk of colorectal cancer after a latent period of about 7-8 years. Even taking into account the “waiting period” during which aspirin had no effect, aspirin prevented about 25 percent of the colorectal cancers. Also in agreement with the epidemiology, there was a reduction in mortality from GI cancers: over 20 years, deaths from these cancers were reduced by about a third in subjects given aspirin.

There were also reductions in death from some other solid cancers (in particular lung cancer), but no apparent benefit in hematological cancers (leukemia, lymphoma, etc.). Longer aspirin use conferred larger benefits, and there were also indications that over the short term, aspirin use reduced the risk of metastatic cancer and cancer death. In some analyses, aspirin even reduced overall mortality.

All good news, but unfortunately questions remain. The trials did not include long-term follow-up of many women, and there wasn't much data about many specific types of cancer. Also, aspirin use after the end of the trials wasn’t recorded. Consequently, we can't use the studies to investigate what happens after aspirin is stopped.

Nonetheless, the picture regarding aspirin and cancer is now very exciting. The drug clearly reduces the incidence and mortality from the important GI cancers, and may similarly affect other cancers. Simply taking a pill seems to prevent cancer and cancer death.

However, just because aspirin may be effective in preventing cancer doesn't mean it necessarily should be used. Aspirin is a real drug, with definite toxicity – in particular GI bleeds and hemorrhagic stroke. This is a particular worry as many of the benefits regarding cancer prevention are delayed for several years - while adverse effects start immediately.

As for any preventive intervention, the benefits of aspirin need to be balanced against these risks. That hasn’t yet been done in an analysis that incorporates the new trial data. However, it is looking more or and more like aspirin will prove to be a winner.

John A. Baron, MD

John A. Baron, MD
Professor of Medicine
University of North Carolina at Chapel Hill