Celecoxib and aromatase activity in breast cancer: Results from a prospective randomized preoperative trial.

Abstract

1527 Background: COX-2 is overexpressed in many epithelial malignancies, including a subset of human breast cancers. Preclinical studies have shown that COX2-derived prostaglandins are a determinant of aromatase expression. Celecoxib, a COX-2 inhibitor, has been studied therapeutically but little is known about its impact on human breast cancer tissue. To determine whether celecoxib has a measurable biologic impact, we investigated whether preoperative administration would alter aromatase activity or Ki67 levels in human breast cancer. Methods: 75 post-menopausal women (median age: 67, range 52-93; 53/75 ER or PR-positive, 9/75 HER2/neu positive)with a proven diagnosis of invasive breast cancer or with highly suspicious masses were prospectively randomized 1:1:1 to each of three groups: no treatment, celecoxib 200 mg bid, or 400 mg bid. Patients were treated for 7-21 days from baseline biopsy or enrollment until definitive surgery. Tissue from biopsy specimens (pretreatment) and surgical specimens (posttreatment) was tested for aromatase activity and Ki67. A subset of patients was accrued with previous core biopsies and repeat baseline core biopsies were not feasible. In these patients, only post treatment tissue from surgical specimens was available for comparison between groups. Results: There were no significant changes in aromatase activity or Ki67 pre- and posttreatment for any group. Similarly, no differences were observed across the three treatment groups. In an exploratory subset analysis, there was no significant difference in aromatase activity levels or Ki67 for HER2/neu-negative vs. positive, or ER/PR-negative vs. positive specimens. Conclusions: We did not observe any significant biologic effect of celecoxib on aromatase activity or Ki67 in patients with invasive breast cancer treated for 1-3 weeks prior to surgery. If celecoxib is an anticancer agent, it is possible that the length of treatment studied here was not sufficient to demonstrate observable changes in Ki67 or aromatase activity. Alternatively it is possible that anticancer activity of celecoxib is exerted through alternative mechanisms and pathways. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Tragara Pharmaceuticals Tragara Pharmaceuticals Pharmacia