A Study to Identify Biomarker Modulation by a Cyclooxygenase-2 (COX-2) Inhibitor in Breast Tissue of Premenopausal Women at High Risk for Estrogen Receptor Negative (ERN) Breast Cancer

OBJECTIVES:

• Determine the change in proliferation in benign breast epithelial cells as measured by Ki-67/MIB-1 in premenopausal women at high risk for estrogen receptor-negative breast cancer treated with celecoxib.
• Determine the feasibility of this regimen by dropout rate of these patients during 12 months of treatment and compliance.
• Determine the proportion of these women likely to express cyclooxygenase-2 protein (COX-2) in at least 10% of benign ductal epithelial cells.
• Compare the success rate of obtaining adequate ductal epithelial cells by random periareolar fine needle aspiration (FNA) and ductal lavage in these patients before vs after 12 months of a prevention intervention.
• Assess pain associated with FNA and ductal lavage in these women.
• Correlate, if possible, serum proteomics pattern with cytologic assessment and mammographic density at baseline and at 12 months in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral celecoxib twice daily. Treatment continues for 12 months in the absence of clinical evidence of cancer confirmed by biopsy or unacceptable toxicity.

Patients are assessed at baseline and at 12 months for mammographic breast density, serum hormone levels, and serum IGF-1/IGFBP-3. Patients undergo ductal lavage or fine needle aspiration for assessment of supernatant proteomics and breast biomarkers.