11056 Background: Aromatase [CYP19] activity and expression is increased by prostaglandin E2, thus providing a rational for combining the COX-2 inhibitor, CELE, with an aromatase inhibitor. To evaluate the effects of these drugs on proliferation and other biomarkers, we conducted a neoadjuvant trial of EXE alone followed by the combination of EXE and CELE. The primary endpoint was the assessment of biomarkers and the secondary endpoint was toxicity. Methods: Clinical stages II/III, postmenopausal, estrogen [ER] and/or progesterone receptor [PR] positive, previously untreated, ECOG 0–1 were eligible. Excluded were inflammatory breast cancer, history of myocardial infarction, and documented allergy to aspirin, NSAIDs, or sulfonamides. After initial core biopsy pts received 8 weeks (wks) of EXE 25 mg daily. They then received a second core biopsy followed by 8 wks of EXE and CELE 400 mg twice daily. After 16 wks, pts had definitive surgery. Compliance was assessed by pill counts at study visists every 4 wks. At baseline, 8, and 16 wks, pts had tumor measurements by physical exam, mammogram, and ultrasound. A tissue microarray [TMA] was contructed and immunohistochemical [IHC] staining with commercially available antibodies for Ki-67, COX-2, HER-2, ER, and PR was performed. Two independent pathologists scored intensity and percentage of cells staining and were blinded to treatment and the timimg of specimen acquistion. Statistical analyses were performed using Wilcoxon signed-rank test Results: Twenty pts with a median age 62 (range 56–87) were enrolled. CELE was discontinued in 3 (15%) pts for grade 1 rash-1 pt; grade 1 creatinine elevation-1 pt; and grade 1 melena-1 pt. Three (15%) pts-partial response, 16 (80%)-stable disease, and 1 (5%)-progressive disease. None of the differences in biomarkers between 0 and 8 wks and 8 and 16 wks were significant. A trend toward decreasing mean Ki 67 was observed from 0 to 8 wks (20% vs 9%, p=0.19) and 8 to 16 wks (9% vs 7%, p=0.7) Conclusions: Neoadjuvant EXE followed by EXE/CELE was well tolerated with anti-tumor activity. Tumor cell proliferation decreased by about 50% during EXE, but small sample size precluded reaching statistical significance. Frozen tissue was collected and the results of CYP 19 mRNA expression will be presented. [Table: see text]
Correlation analysis between expression of PCNA, Ki-67 and COX-2 and X-ray features in mammography in breast cancer
