COX-2 inhibitors may delay onset.(breast cancer)

2002 NOV 14 - (NewsRx.com & NewsRx.net) -- The use of a selective COX (cyclooxygenase)-2 inhibitor (celecoxib) significantly reduced the incidence of breast cancer in HER-2/neu overexpressing mice, according to a study presented October 15, 2002, at the American Association for Cancer Research's (AACR) first annual Frontiers in Cancer Prevention Research meeting.

"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," according to Louise Howe, PhD, assistant professor of cell and developmental biology, Weill Medical College of Cornell University, New York, and lead author of the study.

The study, recently published in AACR's journal, Cancer Research, involved the use of genetically bred HER-2/neu mice that overexpress or overproduce the protein HER-2, a condition that occurs in 20-30% of breast cancer patients and is associated with poor prognosis for the patient. While advances have been made, there are still not enough therapeutic approaches to treat breast tumors that overexpress HER-2/neu.

Recent studies suggest that COX-2, which is overexpressed in about 40% of human breast cancers, may be important for mediating HER-2/neu-induced breast tumor formation. COX-2, an inducible enzyme that generates prostaglandins (PG), may be implicated in several biological events throughout the process of tumor development. Therefore, it may be considered a potential target for preventing and possibly treating a number of cancers, including colorectal and now breast.

The first study, from Weill Medical College, randomly tested 50 mouse mammary tumor virus (MMTV)/neu mice that were fed either a diet containing 500 ppm celecoxib or a control diet. Mammary tumors were detected in 50% of the control mice at 32.3 weeks of age versus 39.6 weeks of age in the celecoxib-treated mice. The incidence of breast tumors was lower at all subsequent ages for the celecoxib-treated mice relative to control mice. This protective effect was achieved at drug levels that can be safely administered in humans.

The study also showed that MMTV/neu mice express COX-2, which is overexpressed in HER-2/neu positive human breast cancers, allowing researchers to investigate the chemopreventive ...