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A Study to Identify Biomarker Modulation by a Cyclooxygenase-2 (COX-2) Inhibitor in Breast Tissue of Premenopausal Women at High Risk for Estrogen Receptor Negative (ERN) Breast Cancer

Phase 2
18 Years
55 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Study to Identify Biomarker Modulation by a Cyclooxygenase-2 (COX-2) Inhibitor in Breast Tissue of Premenopausal Women at High Risk for Estrogen Receptor Negative (ERN) Breast Cancer


- Determine the change in proliferation in benign breast epithelial cells as measured by
Ki-67/MIB-1 in premenopausal women at high risk for estrogen receptor-negative breast
cancer treated with celecoxib.

- Determine the feasibility of this regimen by dropout rate of these patients during 12
months of treatment and compliance.

- Determine the proportion of these women likely to express cyclooxygenase-2 protein
(COX-2) in at least 10% of benign ductal epithelial cells.

- Compare the success rate of obtaining adequate ductal epithelial cells by random
periareolar fine needle aspiration (FNA) and ductal lavage in these patients before vs
after 12 months of a prevention intervention.

- Assess pain associated with FNA and ductal lavage in these women.

- Correlate, if possible, serum proteomics pattern with cytologic assessment and
mammographic density at baseline and at 12 months in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral celecoxib twice daily. Treatment continues for 12 months in the
absence of clinical evidence of cancer confirmed by biopsy or unacceptable toxicity.

Patients are assessed at baseline and at 12 months for mammographic breast density, serum
hormone levels, and serum IGF-1/IGFBP-3. Patients undergo ductal lavage or fine needle
aspiration for assessment of supernatant proteomics and breast biomarkers.

Patients are followed at 2 weeks and then annually for 5 years.

PROJECTED ACCRUAL: A total of 110 patients will be accrued for this study within 10-14

Inclusion Criteria


- Increased risk for breast cancer on the basis of at least 1 of the following

- Five-year Gail risk at least 1.7% or a calculated risk at least 5 times the
average for age group

- 20-29 years old - calculated 5-year Gail risk is at least 0.1%

- 30-39 years old - calculated 5-year Gail risk is at least 1.0%

- 40 and over - calculated 5-year Gail risk is at least 1.7%

- Known BRCA1/BRCA2 mutation carrier

- Family history consistent with hereditary breast cancer, as defined by any of
the following circumstances:

- At least 4 relatives with breast cancer at any age

- At least 2 first-degree relatives diagnosed with breast cancer at age 50 or

- Breast and ovarian cancer diagnosed in the same relative

- At least 2 occurrences of breast cancer and 1 occurrence of ovarian cancer
at any age in the same family

- Prior biopsy exhibiting atypical hyperplasia, lobular cancer in situ, ductal
carcinoma in situ (DCIS)*, or invasive cancer** NOTE: *If DCIS or T1a or T1b
disease was found, at least 2 months must have elapsed since prior surgery
and/or radiotherapy to the involved breast

NOTE: **Prior invasive cancer (T1c, T2, or T3) must have been diagnosed at least 2 years
before study and be estrogen receptor-negative, node negative

- Must have had a random periareolar fine needle aspiration successfully performed
within the past 3 months, with at least 1,000 cells on cytology slide and 3
additional slides for biomarker analysis (1 with at least 500 cells for Ki-67 and 2
with at least 100 ductal cells for estrogen receptors and COX-2)

- Hormone receptor status:

- Estrogen receptor negative



- 18 to 55


- Female

Menopausal status

- Premenopausal, defined as menstrual periods estimated to occur every 21 to 35 days
over the past 6 months

Performance status

- Not specified

Life expectancy

- At least 5 years


- Absolute granulocyte count at least 1,000/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 10 g/dL

- No bleeding diathesis within the past year


- Bilirubin no greater than 2.0 mg/dL

- Albumin at least 3.0 g/dL

- AST and ALT no greater than 2 times upper limit of normal (ULN)

- Alkaline phosphatase no greater than 2 times ULN

- No severe liver disease requiring treatment


- Creatinine no greater than 1.5 mg/dL


- No high blood pressure not controlled by medication

- No history of angina

- No history of cardiovascular disease

- No history of deep vein thrombosis


- No history of pulmonary embolism


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior allergy to sulfa, COX-2 inhibitors, or nonsteroidal anti-inflammatory drugs

- No history of an ulcer requiring treatment

- No history of ulcerative colitis

- No inflammatory bowel disease

- No body mass index > 33

- No history of diabetes

- No prior metastatic malignancy of any kind

- No complications of alcoholism requiring hospitalization

- No concurrent asthma being treated


Biologic therapy

- Not specified


- At least 6 months since prior chemotherapy

Endocrine therapy

- At least 6 months since prior antihormone therapy (e.g., selective estrogen-receptor
modulators or aromatase inhibitors)

- Anticipated use of oral or IV corticosteroids must be less than 2 weeks per year

- No change (stop or start) in hormonal therapy within the past 6 months (e.g.,
estrogen, progesterone, oral contraceptives, or fertility agents)


- See Disease Characteristics

- No prior radiotherapy to the contralateral breast involved in the study treatment


- See Disease Characteristics


- At least 3 weeks since prior aspirin, rofecoxib, celecoxib, other COX-2 inhibitors,

- No concurrent anticoagulants

- No other concurrent NSAIDs

- No chronic angiotensin-converting enzyme inhibitors

- No chronic furosemide*

- No chronic fluconazole*

- No chronic lithium NOTE: *Occasional concurrent use allowed

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Prevention

Principal Investigator

Carol J. Fabian, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Kansas


United States: Federal Government

Study ID:




Start Date:

January 2003

Completion Date:

Related Keywords:

  • Breast Cancer
  • breast cancer
  • Breast Neoplasms



Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center Kansas City, Kansas  66160-7353
Oklahoma University Medical Center Oklahoma City, Oklahoma  73104
Lynn Sage Comprehensive Breast Center at Northwestern Memorial Hospital Chicago, Illinois  60611