Celecoxib in Preventing Breast Cancer in At-Risk Premenopausal Women

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention therapy uses certain drugs to try to prevent the development or recurrence of cancer. Celecoxib may be effective in preventing breast cancer in at-risk women. PURPOSE: Phase II trial to study the effectiveness of celecoxib in preventing breast cancer in premenopausal women who are at risk of developing cancer.

Detailed Description
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OBJECTIVES: 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 months.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: celecoxib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Increased risk for breast cancer on the basis of at least 1 of the following criteria: 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 younger 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 PATIENT CHARACTERISTICS: Age 18 to 55 Sex 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 Hematopoietic 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 Hepatic 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 Renal Creatinine no greater than 1.5 mg/dL Cardiovascular No high blood pressure not controlled by medication No history of angina No history of cardiovascular disease No history of deep vein thrombosis Pulmonary No history of pulmonary embolism Other 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 (NSAIDs) 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 PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy 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) Radiotherapy See Disease Characteristics No prior radiotherapy to the contralateral breast involved in the study treatment Surgery See Disease Characteristics Other At least 3 weeks since prior aspirin, rofecoxib, celecoxib, other COX-2 inhibitors, or NSAIDs 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Celecoxib 400 mg bid<br>Celecoxib 400 mg bid | Drug: celecoxib<br>* Celecoxib daily for 12 months<br>* Other names: Celebrex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer