The use of a COX-2 inhibitor may delay the onset of breast cancer, according to research presented at the American Association for Cancer Reserch's first annual Frontiers in Cancer Prevention Research meeting.

The use of the selective COX-2 inhibitor celeccoxib (Celebrex) significantly reduced the incidence of breast cancer in mice, the researchers reported in the journal Cancer Research.

"Since the use of a selective COX-2 inhibitor caused a significant delay in the onset of breast cancer in mice, there is a potential role for using COX-2 inhibitors to prevent human breast cancer," said Louise Howe, PhD, assistant professor of Cell and Developmental Biology at Cornell University and lead author of the study.

The study involved the use of genetically bred mice that overproduce the protein HER-2 (human epidermal growth factor receptor 2). HER2 is a gene found in every cell of the human body and helps a cell divide. Each healthy breast cell contains two copies of the HER2 gene, which contribute to normal cell function.

If extra copies of the HER2 gene appear in a cell, the gene can cause too many HER2 receptors to appear on the cell surface, referred to as HER2 overexpression or HER2 positive. Cancers that overexpress the HER2 protein grow and spread more rapidly. Recent studies suggest that COX-2, which is overexpressed in about 40 percent of human breast cancers, may be important for causing HER-2 related breast cancer.

Researchers randomly tested 50 genetically engineered mice that were fed either a diet containing 500 ppm (parts per million) celecoxib or a control diet. Mammary tumors were found in 50 percent of the control mice at 32.3 weeks of age versus 39.6 weeks of age in the treated mice. The incidence of breast tumors was lower at all subsequent ages for the treated mice compared with the control mice. This protective effect was achieved at drug levels that can be safely administered in humans.

A second study, conducted at Jefferson Medical College, Thomas Jefferson University, confirmed these findings by evaluating the effectiveness of celecoxib in protecting against the development of spontaneous mammary tumors in genetically bred HER-2 mice.

At four weeks of age, mice were fed a diet supplemented with 900 ppm celecoxib, 64 ppm of a COX-1 inhibitor, or an unsupplemented control diet. The incidence of tumors was significantly lowerin the mice fed celecoxib (74 percent) than the controls (97 percent) and COX-1 mice (91 percent).

Breast tumors began appearing at 142 days in the control mice, at 160 days in the COX-1 mice and at 200 days in the celecoxib mice. The average time for tumor development was 265 days in the COX-1 mice, 266.5 days in the control mice and 291 days in the celecoxib mice. Tumor incidence was significantly less in the celecoxib mice (74 percent) than the controls (97 percent) and COX-1 mice (91 percent).

"The results of our study show that celecoxib protects against the development of spontaneous mammary tumors in mice that overexpress HER-2/neu," said Susan Lanza-Jacoby, PhD, professor of surgery at Jefferson Medical College and lead investigator of the study. "The mice also experienced a significant reduction in the number of tumors, as well as a longer time to disease progression."

Additional research, including human studies, is needed to further define the potential implications of these studies for the treatment of breast cancer.

"Studies should be conducted to determine whether the efficacy of nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors as protective agents varies according to the HER-2/neu status of breast cancer," said Dr. Andrew Dannenberg, Director of Cancer Prevention at New York Presbyterian Hospital-Cornell, New York. "Studies also should concentrate on whether the use of selective COX-2 inhibitors may be more effective in combination with other agents for the treatment of HER-2/neu-overexpressing breast cancers."

Other sources: American Association for Cancer Research