Researchers at the Keck School of Medicine of the University of Southern California, Los Angeles, found that women using Ibuprofen every day for five years or longer were more than 50 percent more likely than non-users to be diagnosed with breast cancer, while women using Aspirin every day for five years or longer were more than 81 percent more likely than non-users to be diagnosed with a certain sub-type of breast cancer.

" We wouldn't say, at this stage, that Ibuprofen or Aspirin would cause breast cancer. There are no reasons we know of for certain, biologically, that would explain that, but findings suggest this area merits further study," says Sarah Marshall, at the Keck School and the study's lead author.

" The most important conclusion from this study is that we found little evidence that Aspirin or other NSAID use reduce breast cancer risk, as suggested by other recent studies," Ronald K. Ross says. " In comparison to other studies, our study was very large and statistically very powerful."

Marshall and her colleagues analyzed data on 114,460 women participating in the California Teachers Study, an expansive examination of cancer among female teachers that is led by researchers at the Keck School and USC/Norris Comprehensive Cancer Center.

All participants were cancer-free when they joined the study in 1995 or 1996.
The researchers asked women about their use of NSAIDs, among many other lifestyle factors. They also asked about women's use of an alternative analgesic, Acetaminophen.

Between 1995 and 2001, 2,391 of the participating women were diagnosed with breast cancer. Researchers looked for any relationships between the use of pain medication and breast cancer risk in participating women.

When they accounted for known breast cancer risk factors-such as women's reproductive histories, body mass index, smoking and race-researchers saw no link between the use of NSAIDs in general and breast cancer risk.

But then they looked a little deeper, examining the type of medication women used, how frequently and for how long. They found that long-term daily Ibuprofen users had a higher risk than non-users of breast cancer. Long-term daily Aspirin users, meanwhile, were at higher risk of a type of breast cancer termed estrogen-receptor- or progesterone-receptor-negative breast cancer.

They saw no link between Acetaminophen use and breast cancer risk.

The researchers did not ask about the dose of the medications women had used. Nor did they ask about other NSAIDs such as Naproxen, Celecoxib ( Celebrex ) or Rofecoxib ( Vioxx ), since such medications were not widely available at the time. They plan to ask about additional NSAID use in a follow-up questionnaire.

NSAIDs suppress the expression of the cyclooxygenase 2, or COX-2, gene, researchers explain. The COX-2 gene kicks into gear in wounded or inflamed tissue, so suppressing the gene's expression ( through NSAIDs ) can lower inflammation and associated pain.

Elevated COX-2 levels also are associated with increased formation of blood vessels, increased production of estrogen and reduced apoptosis ( cell death ), all of which might stimulate cancer growth. Researchers have found evidence that NSAID use is linked to decreased risk of cancers of the colon, rectum, ovary, stomach and other sites.

The researchers are unsure why NSAIDs might be associated with increased breast cancer risk. " There may be something else going on with this group of women-women who are high users of NSAIDs," Marshall says. " It could be that they have some other risk factor in common that we have not been able to measure. "

Researchers also suspect that COX-2's significance may vary according to tissue type. COX-2 is expressed in high levels in colorectal cancer, but it may be less important in breast cancer.

Marshall notes that further study is needed, and cautions women from jumping to conclusions. " There's no reason for women to change their pain medication based on the results of this study. There are well-known benefits of taking low-dose aspirin regularly, for example, in terms of preventing cardiovascular disease," she says.

The study has been published in Journal of the National Cancer Institute.

Source: University of Southern California, 2005


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