A new study strengthens the evidence that ibuprofen and other nonsteroidal
anti-inflammatory drugs (NSAIDs) reduce the risk of breast cancer in some
Researchers at Ohio State University's Comprehensive Cancer Center have
found that the activity of the gene responsible for the production of an
enzyme involved in inflammation is increased in tumors from breast cancer
patients compared to normal breast tissues.
The gene, cyclooxygenase-2 (COX-2), produces an enzyme important for
the production of prostaglandins, which play a major role in the process
of inflammation. Prostaglandins have been found in high levels in both
breast and colon cancer cells, and their production has been linked to
the ability of tumors to spread. Nonsteroidal anti-inflammatory drugs,
such as ibuprofen, work by blocking the COX-2 enzyme, which is how these
drugs help control inflammation.
"This is the first time that this gene, which is the target for
NSAIDs activity, has been linked to breast tumors," said Fredika Robertson,
associate professor of microbiology and immunology at Ohio State, and the
investigator who led the study, which was published in the March issue
of the International Journal of Oncology.
NSAIDs May be Effective Chemopreventive Agents
"It also suggests that nonsteroidal anti-inflammatory drugs may
be effective chemopreventive agents in women who have primary breast cancer."
One of the researchers involved included Randall Harris, acting director
of the School of Public Health at Ohio State. Harris, who is also associate
director of cancer control and prevention at Ohio State's Comprehensive
Cancer Center, published two case-control studies in 1995 and 1996 suggesting
that women who take NSAIDs at least once every other day for 5 years or
more reduce their risk of breast cancer by 40%, as compared with women
who do not take the drugs.
"Taking the epidemiology data together with the molecular data
revealed by this study indicates that NSAIDs may reduce the risk of recurrence
in women who have received treatment for primary breast cancer," said
Nonsteroidal anti-inflammatory drugs are already known to inhibit the
growth of colon tumors and precancerous polyps in the colon, and they are
showing promise in clinical trials for reducing the risk of recurrent colon
cancer. Levels of COX-2 are also high in colon cancer.
The present study looked at 13 breast cancer tumors and 3 samples of
matched normal tissue. The researchers have since increased the number
of tumors sampled to 30 and normal tissues to 8. The number of normal tissues
is low because these samples are more difficult to obtain.
The researchers rated the tumor samples according to the degree of inflammation
present to determine if inflammation was responsible for the level of COX-2
gene activity. They found that the two were unrelated.
COX-2 Activity Linked to Tumor Invasiveness
"We found the highest levels of COX-2 activity in tumors that were
invasive and that showed no evidence of inflammation," said Robertson.
The researchers found that the higher the number of cancer cells present
in the tumor, the higher the level of the COX-2 enzyme present in tumor
tissue (normal breast cells and connective tissue cells are also found
in breast tumors).
Lower-grade tumors, which have fewer cancer cells, have somewhat elevated
COX-2 activity, but the level of activity is lower than in high-grade tumors.
Thus far, normal breast tissues have shown no COX-2 activity.
Overall, the results came as a surprise, said Robertson. "We had
no idea we would find such a highly significant association between tumor
invasiveness, tumor grade, and COX-2 activity."