Neoadjuvant therapy with celecoxib to women with early stage breast cancer.
Cyclooxygenase-2 (COX-2) is preferentially expressed in breast cancer cells compared to normal breast tissue. COX-2 inhibitors are, therefore, potential therapeutic options for patients with breast cancer. Women newly diagnosed with non metastatic breast cancer were enrolled into the study after undergoing a diagnostic core needle biopsy. Patients received celecoxib treatment at 400 mg orally twice a day for 14 days, and then underwent surgical excision of their tumor. Core biopsies obtained at the time of initial diagnostic procedure and surgical excision specimens were stained for Ki-67, as well as COX-2 and cleaved poly (ADP-ribose) polymerase (PARP) expression (as an apoptosis marker). Appropriate negative and positive controls were included. We assessed the difference in Ki-67, COX-2 and cleaved PARP expression levels, before and after treatment using the Wilcoxon's matched-pair ranks test and the McNemar's test with continuity correction. Sixteen patients were enrolled. The median age was 54 years. ER and/or PR expression was present in 81% of tumors; Her-2 neu overexpression was present in 25%. No significant change in COX-2 or cleaved PARP expression was noticed in the post intervention specimen compared to the core biopsies. Surprisingly, there was a significant increase in the Ki-67 expression (p < 0.009). This short term prospective study was conducted to assess the effects of celecoxib, on the proliferative and apoptotic indexes in patients with early stage breast cancer. We have found an increase in the Ki-67 activity, with no significant down regulation of COX-2 or increase in cleaved PARP expression with 14 days of therapy. This could be partly due to the small sample size.
Tfayli
A
A
University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. arafat-tfayli@ouhsc.edu
Yang
J
J
Kojouri
K
K
Kesserwan
C
C
Jafari
M
M
Ozer
H
H
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000032:analysis; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
D052246:Cyclooxygenase 2 Inhibitors; D019394:Ki-67 Antigen; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011065:Poly(ADP-ribose) Polymerases; D000068579:Celecoxib