COX-2 expression is marker for cancer development in some benign breast biopsies

t’s a good news, bad news situation. Some women who have a breast biopsy are told that while they don’t have cancer, they do have atypical hyperplasia - cells that aren’t quite normal and might become cancerous someday. This happens to one-fourth of women undergoing breast biopsies but no one knows which individuals are at risk.

In their quest to discover who is at risk, researchers at Mayo Clinic are building a biopsy profile to try to predict cancer outcome, and in the March 11 online edition of the Journal of the National Cancer Institute, they report finding a new variable to add to this profile.

The research team discovered that women whose atypia tissue expressed COX-2 enzymes were more likely to develop breast cancer subsequently, and that the more the enzyme expressed, the higher the risk.

Specifically, 20 years after a biopsy in which atypia was found, 31 percent of women with high levels of COX-2 in their atypia sample had developed breast cancer, versus 14 percent of those with no COX-2 expression. For those with moderate levels of COX-2, 24 percent had developed breast cancer.

“Based on these findings, COX-2 expression in atypia may be a biomarker of risk of progression to breast cancer,” says the study’s senior investigator, Mayo Clinic oncologist Lynn Hartmann, M.D. “COX-2 is a relevant candidate because it drives a number of malignant features and has been shown to be important in breast cancer.

“Each year in the United States, about 1 million women have a benign breast biopsy; and some of them receive the worrisome news that they have atypical hyperplasia,” Dr. Hartmann says. If other studies validate these findings, she notes that one strategy to help manage patients may be to use a COX-2 inhibiting agent, such as celecoxibor rofecoxib, to prevent breast cancer from developing. “This study raises the possibility of targeting COX-2 in selected women to reduce their risk of breast cancer,” she says.

In the biopsy profile thus far, the Mayo risk model includes age, the number of regions of atypical cells in the biopsy, COX-2 expression and the status of the normal lobules in the breast.

“Our goal is to individualize risk for breast cancer so that we can provide effective care and risk reduction for each of our patients,” says Dr. Hartmann.

Cyxlooxygenase (COX) enzymes produce prostaglandin compounds responsible for pain and inflammation, and nonsteroidal anti-inflammatory drugs (NSAIDs) are designed to reduce expression of COX enzymes, although some NSAID use has been associated with side effects (most notably possible kidney failure). COX-2 is a form of COX that is not usually found in normal tissues but which has been associated with several cancers, including ductal carcinoma in situ and invasive breast cancers.

In this study, researchers examined breast biopsy samples that contained atypia for COX-2 expression which has never been done before.