9 April 2003 10:00 GMT

by Damaris Christensen

Data from two independent US research groups have added weight to the theory that so-called non-steroidal anti-inflammatory drugs (NSAIDs), a group of drugs that includes aspirin, could lower the risk of developing different types of cancer.

Women who regularly use over-the-counter painkillers like ibuprofen and aspirin are significantly less likely to develop breast cancer than are women who do not use such medications, report researchers at Ohio State University in Columbus. Previous studies in this area have had mixed results, some showing a benefit and others no effect for taking the drugs.

In this latest study, women who took three or more NSAID tablets each week for five to nine years reduced their risk of developing breast cancer by 21%, said lead researcher and epidemiologist Randall Harris. Women who took these regular doses of NSAIDs for ten or more years had a 28% reduction in their chance of developing breast cancer, he added.

This reduction held even among women who were judged at high risk of developing breast cancer because they were overweight, had a strong family history of the disease, or did not exercise, he says. "The results suggest that even women at high risk for breast cancer may be protected by taking NSAIDs," said Harris. While it is too early to make specific recommendations, he says that women over 40 might consider taking a dose every day. He himself follows that advice.

Raymond DuBois, director of cancer prevention with the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Tennessee, studies NSAIDs as possible treatments for colon cancer. He notes that Harris' study is large and well designed, but cautions that until prospective trials are completed it is difficult to determine the risk-benefit of NSAID therapy to prevent cancer.

Regular NSAID use may lead to side effects such as gastrointestinal bleeding and, rarely, stroke, Harris warns. "Some people aren't at risk of developing these diseases in the first place, so they should not take these preventive measures," he said, adding that people should consult their physicians before taking NSAIDs.

Harris presented his findings at a press briefing on Tuesday organized in lieu of last week's cancellation of the American Association for Cancer Research Annual Meeting, where the data were due to have been presented.

Ibuprofen was more effective than aspirin in reducing breast cancer, Harris reports. Using ibuprofen for ten or more years led to an almost 50% reduction in breast cancer compared with women who did not use any NSAIDs. Low-dose aspirin, or baby aspirin, had no effect, nor did the use of the pain reliever acetaminophen. The latter finding is unsurprising, he says, because acetaminophen does not reduce inflammation or block COX-2, an enzyme implicated in cancer development.

Among more than 80,700 women enrolled in the Women's Health Initiative - an observational study of women between 50 and 79 years old - 1,392 were diagnosed with breast cancer within four years of the study's launch. About a third of subjects took NSAIDs regularly - defined as a standard dose (200 mg of ibuprofen or 325 mg of aspirin, for example) at least three times a week. None of the women had cancer at the baseline of the study. The annual incidence of breast cancer in the study - calculated at 481 cases per 100,000 women followed each year - is similar to the average incidence of breast cancer in the US each year. About 185 cases of breast cancer might have been prevented each year with regular use of NSAIDs, Harris says.

A variety of animal studies suggest that NSAIDs may prevent, or potentially treat, a variety of cancers, including cancer of the colon, breast, lung, esophagus, ovary and prostate. The evidence for the benefit of NSAIDs is strongest in colon cancer. An NSAID called celecoxib, which specifically blocks COX-2, is already approved as a preventative therapy for those with a high risk of developing colon cancer.

In other news released at Tuesday's briefing, researchers from the Institute for Cancer Prevention at the American Health Foundation-Cancer Center in Valhalla, New York, reported that relatively low-doses of a COX-2 inhibitor paired with a component of fish oil called docosoheanoic acid (DHA), may prevent and even treat colon cancer. Both DHA and celecoxib block COX-2 expression and activity.

The effect of the two compounds together was synergistic, says lead researcher C.V. Rao. In the study, researchers treated human colon cancer cells with either celecoxib or DHA alone as well as with several concentrations of celecoxib - a selective COX-2 inhibitor - in combination with DHA. In isolation, more than 100 micromolar concentrations of celecoxib, and more than 150 micromolar concentrations of DHA, were required to inhibit cell growth and induce cell death. In combination, the doses could be dropped to 50 micromolar celecoxib and 75 micromolar DHA while maintaining the cancer-cell-damaging effects.

"This work is done in a cell line, so it is very preliminary," said Ernest Hawk, chief of GI cancer prevention research at the National Cancer Institute in Bethesda, Maryland. In addition, he cautioned, the 'low-dose' concentration of celecoxib in this study is probably higher than the effective concentration in cancer tissues of people who take regular doses of the drug. However, he told BioMedNet News that he was "very enthusiastic" about the approach of using combinations of agents in preventing cancer, especially combinations of drugs and dietary agents.