New Evidence That NSAIDs Reduce Breast Cancer Risk

A new study strengthens the evidence that ibuprofen and other nonsteroidalanti-inflammatory drugs (NSAIDs) reduce the risk of breast cancer in somewomen.

Researchers at Ohio State University's Comprehensive Cancer Center havefound that the activity of the gene responsible for the production of anenzyme involved in inflammation is increased in tumors from breast cancerpatients compared to normal breast tissues.

The gene, cyclooxygenase-2 (COX-2), produces an enzyme important forthe production of prostaglandins, which play a major role in the processof inflammation. Prostaglandins have been found in high levels in bothbreast and colon cancer cells, and their production has been linked tothe ability of tumors to spread. Nonsteroidal anti-inflammatory drugs,such as ibuprofen, work by blocking the COX-2 enzyme, which is how thesedrugs help control inflammation.

"This is the first time that this gene, which is the target forNSAIDs activity, has been linked to breast tumors," said Fredika Robertson,associate professor of microbiology and immunology at Ohio State, and theinvestigator who led the study, which was published in the March issueof the International Journal of Oncology.

NSAIDs May be Effective Chemopreventive Agents

"It also suggests that nonsteroidal anti-inflammatory drugs maybe effective chemopreventive agents in women who have primary breast cancer."

One of the researchers involved included Randall Harris, acting directorof the School of Public Health at Ohio State. Harris, who is also associatedirector of cancer control and prevention at Ohio State's ComprehensiveCancer Center, published two case-control studies in 1995 and 1996 suggestingthat women who take NSAIDs at least once every other day for 5 years ormore reduce their risk of breast cancer by 40%, as compared with womenwho do not take the drugs.

"Taking the epidemiology data together with the molecular datarevealed by this study indicates that NSAIDs may reduce the risk of recurrencein women who have received treatment for primary breast cancer," saidRobertson.

Nonsteroidal anti-inflammatory drugs are already known to inhibit thegrowth of colon tumors and precancerous polyps in the colon, and they areshowing promise in clinical trials for reducing the risk of recurrent coloncancer. Levels of COX-2 are also high in colon cancer.

The present study looked at 13 breast cancer tumors and 3 samples ofmatched normal tissue. The researchers have since increased the numberof tumors sampled to 30 and normal tissues to 8. The number of normal tissuesis low because these samples are more difficult to obtain.

The researchers rated the tumor samples according to the degree of inflammationpresent to determine if inflammation was responsible for the level of COX-2gene 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 wereinvasive and that showed no evidence of inflammation," said Robertson.

The researchers found that the higher the number of cancer cells presentin the tumor, the higher the level of the COX-2 enzyme present in tumortissue (normal breast cells and connective tissue cells are also foundin breast tumors).

Lower-grade tumors, which have fewer cancer cells, have somewhat elevatedCOX-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 hadno idea we would find such a highly significant association between tumorinvasiveness, tumor grade, and COX-2 activity."