HOW TO PREVENT CANCERS

This week on the NY Times Well Blog is a discussion of whether the health benefits of aspirin have been oversold (or the health risks underreported). The spark to this renewed discussion is a Cochrane review of the aspirin data. What gets lost in the debate, is how important timing is when considering the health benefits of aspirin use. As we've previously noted here on CNiC, the benefits of aspirin use for colorectal cancer risk reduction and reduction in colorectal cancer mortality really become apparent after a decade or more of use. With a mean follow-up of 6 years, the latest review by Seshasai et al, wouldn't capture the full benefit of regular aspirin use.

The documented benefits of aspirin go back, literally, thousands of year.  As early as the fifth century B.C., Hippocrates noted that a bitter willow bark extract - which contained chemicals very similar to today's aspirin - was effective at relieving pain.  Since then, aspirin has become the most commonly used medicine in the world, and its benefits have been shown to reach well beyond pain relief to include the prevention of heart attack, stroke, and now cancer.

Studies have shown for a number of years that taking a daily aspirin could lower the risk of developing and dying of colon cancer, with the latest large analysis by Rothwell and colleagues finding a 25 percent drop in the risk of developing the disease, and a 35 percent risk of dying from it, with as little as 75mg of aspirin a day (previous post; study).

Now, a new analysis by Rothwell and colleagues - which combined data on over 25,000 participants in eight randomized controlled trials - shows big reductions in the risk of cancer deaths with aspirin use, not only for colon cancer, but for a broad range of individual cancers, and for cancer overall (study).   Daily aspirin use for five or more years lowered the risk of cancer death overall by 34 percent compared to placebo.

Strikingly, the benefits persisted, and even expanded, long after the end of the trials and the aspirin treatment.  After up to 20 years of follow-up, overall cancer deaths were 22 percent lower in the aspirin group compared to placebo.  The risk of esophageal cancer death was 58 percent lower.  The risk of colorectal cancer death was 40 percent lower, and lung cancer deaths nearly 30 percent lower.

In general, the longer the daily aspirin use, the more robust the cancer benefits.

The findings of this latest study, combined with all the previous ones, could possibly rebalance the discussion of the risks and benefits of aspirin use.  When looking at aspirin's benefits in the past, the focus was largely on the heart benefits, and while these benefits could be substantial, they still needed to be balanced with the risks that go along with aspirin use, most commonly an increased risk of bleeding in the GI tract and possibly the brain.

With long term demonstrated benefits in lowering cancer deaths, which persist even after daily aspirin use of 5 - 10 years, the balance may be tipping toward the benefits of aspirin outweighing the risks for a broader swath of the population than is currently recommended (which is largely limited to those at high risk of heart attack).

At the cost of just pennies a day, it may just be what the doctor ordered.

Related CNiC Posts
Aspirin
Data Snapshot

New evidence has emerged that adds further insight into the risks and benefits of aspirin for prevention of colorectal cancer. Aspirin has been extensively studied in observational epidemiologic settings that address duration of use, dose, and magnitude of risk reduction. The observational evidence is consistent with evidence from randomized primary prevention trials, which have shown that use of at least 300 mg of aspirin per day for at least 5 years is effective in preventing colon cancer, reducing risk by about 25% (Flossmann and Rothwell 2007). A latency of about 10 years is observed. Like all chemoprevention strategies, risks and benefits must be balanced (Glasziou and Irwig 1995). To date, the risk-benefit considerations of cardiovascular disease, bleeding complications, stomach pain, and heartburn have precluded recommendations for aspirin use as a widespread prevention strategy (Gralow, Ozols et al. 2008; Cuzick, Otto et al. 2009).

In the Lancet, a new study combining data from four randomized trials of aspirin versus control in both primary and secondary prevention of vascular events evaluated risk of colorectal cancer over 20 years (study). A fifth trial compared doses of aspirin. After combining the data on individuals in these five trials the investigators observed that aspirin use reduced the 20-year risk of colon cancer but not rectal cancer. Risk of cancer was reduced by 25% and colon cancer mortality was reduced by 35%. Similar to previous reports, benefit of aspirin use increased with duration of use indicating that aspirin use operates early in the pathway to colon cancer and leading to long-term therapy as the necessary approach for prevention of colon cancer. This study, in contrast with previous evidence suggests that the benefit for colon cancer prevention is obtained with as little as 75 mg per day.

Importantly, this study separately evaluated colon cancer rectal cancers. We have previously shown that the risk factors for these two cancers sites vary substantially (Wei, Giovannucci et al. 2004). The evidence for aspirin adds further support for strategies to be specific to risk, particularly among those who are at increased risk, as is the case for family history.