Celecoxib in Treating Postmenopausal Women Who Are Undergoing Surgery for Invasive Breast Cancer

An Exploratory, Open-Label Phase I Pharmacodynamic Study of COX-2 Inhibition With Celecoxib (Celebrex) and Aromatase Activity in Breast Cancer

This randomized phase I trial is studying the side effects of celecoxib in treating postmenopausal women with invasive breast cancer who are scheduled to undergo surgery at Memorial Sloan-Kettering Cancer Center. Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

PRIMARY OBJECTIVES:

I. Determine whether celecoxib suppresses aromatase activity in postmenopausal women with invasive breast cancer planning to undergo surgery.

SECONDARY OBJECTIVES:

I. Correlate celecoxib-mediated inhibition of aromatase activity with levels of cyclooxygenase (COX)-2 and HER-2/neu and estrogen receptor status in these patients.

II. Determine the effect of this drug on histology, Ki67, RNA expression profile by microarray analysis, PI3-K, AKT and ERK1/2 MAP kinase activities, and PGE_2 levels in these patients.

III. Determine whether any observed biological effect of this drug is dose-dependent in these patients.

IV. Identify collateral targets (COX-2-independent) of this drug in these patients.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive oral celecoxib twice daily for 1-3 weeks (according to the duration between biopsy and surgery) in the absence of unacceptable toxicity.

Arm II: Patients receive a higher dose of oral celecoxib as in arm I.

Arm III: Patients do not receive treatment.

All patients undergo definitive surgery.

PROJECTED ACCRUAL: A total of 75 patients (25 per treatment arm) will be accrued for this study within 2-3 years.

Inclusion Criteria:

• Histologically confirmed invasive breast carcinoma

  • Tumor at least 1 cm by radiologic estimate or physical exam
  • No disease limited to ductal carcinoma in situ only

• Planning to undergo surgery at Memorial Sloan-Kettering Cancer Center

• Hormone receptor status:

  • Not specified

• Female

• Postmenopausal as defined by at least 1 of the following:

  • No menstrual period within the past 12 months
  • Prior bilateral oophorectomy

• No known liver disease

• No renal insufficiency

• No congestive heart failure

• No coronary artery disease

• No history of documented peptic ulcer disease

• No gastritis

• No medical condition that would preclude definitive surgery

• No allergy to NSAIDs or sulfa-containing drugs

• No connective tissue diseases, including any of the following:

  • Systemic lupus erythematosus
  • Reynaud's disease
  • Scleroderma

• More than 3 months since prior chemotherapy

• More than 2 weeks since prior hormone replacement therapy

• More than 2 weeks since prior tamoxifen

• More than 2 weeks since prior aromatase inhibitors

• More than 2 weeks since prior raloxifene

• More than 2 weeks since prior steroids

• More than 1 week since prior nonsteroidal anti-inflammatory drugs (NSAIDs)

• More than 1 week since prior cyclooxygenase (COX)-2 inhibitors

• No concurrent warfarin

• No concurrent thiazide or loop diuretics

• No concurrent COX-2 inhibitors

• No concurrent NSAIDs