Phase II trial of neoadjuvant exemestane in combination with celecoxib in postmenopausal women who have breast cancer

Clin Breast Cancer. 2011 Aug;11(4):221-7. doi: 10.1016/j.clbc.2011.03.022. Epub 2011 May 19.

Abstract

Purpose: 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).

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstadienes / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Carcinoma, Lobular / drug therapy*
  • Carcinoma, Lobular / secondary
  • Celecoxib
  • Cyclooxygenase 2 / chemistry
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Postmenopause / drug effects*
  • Pyrazoles / therapeutic use*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Sulfonamides / therapeutic use*
  • Survival Rate
  • Treatment Outcome

Substances

  • Androstadienes
  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Pyrazoles
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Sulfonamides
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Receptor, ErbB-2
  • Celecoxib
  • exemestane