title: Phase II trial of neoadjuvant exemestane in combination with celecoxib in postmenopausal women who have breast cancer.
abstract: OBJECTIVE
  Within breast tissue, aromatase expression and activity is increased by prostaglandin E2, providing a rationale for combining the COX-2 inhibitor celecoxib with an aromatase inhibitor. To evaluate the effect of these drugs on aromatase and other biomarkers, a phase II trial of neoadjuvant exemestane followed sequentially by celecoxib plus exemestane was performed.
  
  
  METHODS
  Postmenopausal women with estrogen receptor (ER) and/or progesterone (PR) positive stages II-III breast cancers received 8 weeks of exemestane 25 mg daily, followed by 8 weeks of exemestane 25 mg daily and celecoxib 400 mg twice daily. Core biopsies were collected pretreatment, after 8 weeks of exemestane, and at definitive breast cancer surgery. A tissue microarray was constructed and immunohistochemistry (IHC) for aromatase, ER, PR, HER-2, Ki-67, and COX-2 was performed.
  
  
  RESULTS
  Twenty-two women were enrolled. Celecoxib was discontinued in 4 (18%) women for toxicity (all grade 1 and 2) and 2 (9%) developed serious cardiac events occurring at 1 and 4 months after completing treatment. By US, there were 8 (36%)-partial responses and 12 (55%)-stable disease. There were no pathological complete responses (pCR). There were statistically significant decreases in ER (P = .003), PR (P = .002), Ki-67 (P < .001), and COX-2 (P = .004) expression. No significant differences in aromatase or HER-2 expression were observed (P = .13 and P = .39, respectively).
  
  
  CONCLUSIONS
  The addition of celecoxib to exemestane was tolerated by the majority of women and anti-tumor response was observed. Additional studies, including gene expression, are required to more fully understand the basis for the decreased expression of ER, PR, Ki-67, and COX-2.
authors: Comprehensive Breast Health Services of the Ohio State University Medical Center, and James Cancer Hospital, 320 West 10th Avenue, Columbus OH 43210-1240, USA.
authors: Maryam B
authors: MB
authors: Lustberg
authors: Stephen P
authors: SP
authors: Povoski
authors: Weiqiang
authors: W
authors: Zhao
authors: Rebecca M
authors: RM
authors: Ziegler
authors: Yasuro
authors: Y
authors: Sugimoto
authors: Amy S
authors: AS
authors: Ruppert
authors: Amy M
authors: AM
authors: Lehman
authors: Donna R
authors: DR
authors: Shiels
authors: Ewa
authors: E
authors: Mrozek
authors: Bhuvaneswari
authors: B
authors: Ramaswamy
authors: Rachel M
authors: RM
authors: Layman
authors: Robert W
authors: RW
authors: Brueggemeier
authors: Charles L
authors: CL
authors: Shapiro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000556:secondary; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D017698:Postmenopause / Q000187:drug effects*; D011720:Pyrazoles / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013449:Sulfonamides / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013449:Sulfonamides; C496540:PTGS2 protein, human; C056516:exemestane