Findings reported July 13 at the annual meeting of the American Association of Cancer Research in Washington, D.C., indicate that using ibuprofen – a non-steroidal anti-inflammatory drug (NSAID) – on a regular basis for more than 10 years may decrease a woman's chance by nearly 50 percent that she will develop breast cancer.
Using aspirin – another NSAID – reduced breast cancer risk by about 22 percent, said Randall Harris, the study's lead author and the co-director of the Center of Molecular Epidemiology and Environmental Health at Ohio State University.
He and his colleagues used data from a survey that followed nearly 81,000 women for four years to determine what effect NSAIDs had on decreasing the incidence of breast cancer. These women were some of more than 100,000 women participating in the Women's Health Initiative, an ongoing nationwide study sponsored by the National Institutes of Health that looks at a variety of women's health issues.
"We're discovering that these compounds – NSAIDs – aren't just for pain and inflammation relief," said Harris, who is also the co-principal investigator of the Women's Health Initiative clinical center at Ohio State. "This study shows that these drugs also have significant anticancer effects."
The NSAIDs examined in this study included over-the-counter medications such as ibuprofen and aspirin.
At the outset of this study, 80,741 postmenopausal women aged 50 to 79 were asked how often and for how long they had used NSAIDs. These women were selected because they had no personal history of cancer.
Each participant was also asked a series of questions that helped researchers evaluate her risk of developing breast cancer – questions such as how often she exercised, her body mass, if she had ever given birth, if she was on estrogen therapy, and if she had a family history of cancer. The researchers put the women into two groups: those who reported taking NSAIDs on a regular basis – two or more tablets a week – and those who either seldom or never took NSAIDs.
The participants completed health interviews yearly for four years. During that time, 1,392 women – or 1.7 percent of those enrolled in the study -- developed breast cancer.
Women who regularly took NSAIDs for five to nine years had a 21 percent reduction in the incidence of breast cancer. Women taking these drugs on a regular basis for 10 or more years had a 28 percent reduction in the risk of developing the disease. It wasn't until the researchers separated these women further into groups based on the type of NSAID they took that the effect of ibuprofen vs. aspirin became clear.
"The results suggest that there were about 150 fewer breast cancer cases per 100,000 women each year among NSAID users vs. those who didn't use NSAIDs," Harris said. "This translates into an approximately 30 percent reduction for all NSAID users, and a 50 percent reduction in risk among ibuprofen users."
Even women in high-risk groups – those who were obese, those who had never given birth or gave birth later in life, those with a family history of breast cancer, etc. – still had the same level of reduction if they were regular NSAID users.
Harris thinks the reason that NSAIDs – particularly ibuprofen – have such a powerful effect is due to their ability to block the inflammatory process. Scientists believe these drugs block the gene responsible for triggering inflammation in the body. For unknown reasons, this gene, COX-2, is inappropriately turned on – and stays on – in breast and other types of cancer.
"We think that NSAIDs turn off unnecessary inflammation by blocking COX-2," Harris said. "Toning down this kind of dysfunctional, uncontrolled inflammation can block critical steps in tumor development, such as cell division, the growth of new blood vessels and the spread of the tumor to other areas of the body.
"I don't know what turns COX-2 on, or why it gets stuck in the on position. But it's bad news if it does get stuck, because it motivates all these steps to carcinogenesis."
Evidence is mounting that NSAIDs may also help in the treatment and prevention of other cancers.
"There's too much converging and compelling evidence to deny the effects of NSAIDs," Harris said. "Most malignant tumors, including colon, breast, prostate, and lung, appear to be inhibited by NSAID use."
These drugs may have side effects in a small percentage of people, said Harris, the most common of which is an upset or irritated stomach.
"If you're going to be a regular ibuprofen or aspirin user, tell your physician," he said, adding that he takes 200 mg of ibuprofen daily.
"There is no recommended guideline for when or if to start taking NSAIDs," he continued. "The evidence is compelling that these compounds do protect women who are 40 and older, but they need to be taken for a few years. It's the sustained inhibition of COX-2 that impedes the risk of carcinogenesis."
Harris has worked on the link between NSAIDs and breast cancer since the late 1980s. He and his colleagues also suspect that NSAIDs may have a role in treating or helping to prevent other cancers, such as colon, prostate and lung cancers.
This research was originally scheduled for presentation in April at the American Association of Cancer Research meeting in Toronto. That meeting was rescheduled due to the SARS epidemic.
Harris conducted this study with Ohio State researchers Rebecca Jackson and David Frid; Rowan Chlebowski, of the Harbor-UCLA Research and Education Institute; Garnet Anderson, Emily White and Anne McTiernan, Aimee Sparks and Rebecca Rodabaugh, all with the Fred Hutchinson Cancer Research Center in Seattle; and Joao Ascenseo, of George Washington University in Washington, D.C.
[EDITOR'S NOTE: This work was scheduled to be reported in April at the annual meeting of the American Association of Cancer Research. However, that meeting was postponed due to concerns over the emerging SARS prevalance in Toronto. It is Ohio State's policy to report only those research findings that have been published in peer reviewed journals or presented at major professional meetings. Since the AACR meeting did not occur until last week, we delayed our reporting of these findings.]
Contact: Randall Harris, 614-293-3903; Harris.44@osu.edu
Written by Holly Wagner, 614-292-8310; Wagner.235@osu.edu