s0300, celecoxib in preventing breast cancer in premenopausal women

Conditions: Breast Cancer

Summary: rationale: chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. the use of celecoxib may be effective in preventing breast cancer. purpose: this randomized phase ii trial is studying how well celecoxib works in preventing breast cancer in premenopausal women who are at risk for developing the disease.

objectives: * compare 1-year mammographic density in premenopausal women at high risk for developing breast cancer treated with celecoxib vs placebo. * compare 1-year proliferation of breast epithelial cells, as measured by ki67 staining, in patients treated with these drugs. * compare the expression of other biomarkers, including cyclo-oxygenase-2 (cox-2) enzyme and a marker of apoptosis, in breast tissue of patients treated with these drugs. * compare 1-year plasma levels of insulin-like growth factor (igf)-1, igf binding protein-3, and prostaglandin e_2 in patients treated with these drugs. * compare the toxicity of these drugs in these patients. outline: this is a randomized, placebo-controlled, double-blind, multicenter study. patients are stratified according to risk category (lobular carcinoma in situ or ductal carcinoma in situ vs brca1/2 mutation and any gail risk vs gail risk ≥1.7% but \< 5% vs gail risk ≥ 5%) and prior tamoxifen use (yes vs no). patients are randomized to 1 of 2 treatment arms. * celocoxib: patients receive oral celecoxib twice daily. * placebo: patients receive oral placebo twice daily. in both arms, treatment continues for 12 months in the absence of unacceptable toxicity or diagnosis of cancer. patients are followed at 1 month. projected accrual: a total of 100 patients (50 per treatment arm) will be accrued for this study.

Eligibility criteria:
disease characteristics: * at elevated risk of developing breast cancer, as defined by 1 of the following: * modified gail risk at 5 years ≥ 1.7% or lifetime risk ≥ 20% and claus model, brcapro model, or tyrer-cuzick model lifetime risk ≥ 20% * diagnosis of lobular carcinoma in situ or ductal carcinoma in situ * known deleterious mutation of brca1 or brca2 * at least 1 breast available for imagery and biopsy * has undergone a baseline mammogram with a standard density wedge within 7-14 days after completion of the last menstrual period and within 7 days before study entry * mammogram normal or benign (birads score 0 or 1) * hormone receptor status: * not specified patient characteristics: age * 18 and over sex * female menopausal status * premenopausal, defined by 1 of the following criteria: * last menstrual period \< 6 months ago and no prior bilateral ovariectomy and not on estrogen replacement therapy * prior hysterectomy (with ovaries still in place) and normal follicle-stimulating hormone levels within 28 days of study entry performance status * zubrod 0-1 life expectancy * not specified hematopoietic * not specified hepatic * bilirubin \< 2.0 times institutional upper limit of normal (iuln) * sgot or sgpt \< 2 times iuln * alkaline phosphatase \< 2 times iuln * inr ≤ 1.5 * pt and ptt ≤ iuln renal * serum creatinine \< 2.0 times iuln cardiovascular * no history of myocardial infarction * no angina pectoris * no known coronary artery disease * no history of stroke or mini-stroke (e.g., transient ischemic attack) * no history of thromboembolic disease (e.g., deep vein thrombosis or pulmonary embolism) * no uncontrolled hypertension (i.e., blood pressure \> 140/90 mmhg) pulmonary * no asthma after taking aspirin or other nsaids other * no known sensitivity to celecoxib * no allergy to sulfonamides * no urticaria or allergic-type reactions after taking aspirin or other nsaids * no extreme lactose intolerance * no other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or early bladder cancer (preinvasive transitional cell carcinoma of the bladder) * not pregnant or nursing * fertile patients must use effective contraception prior concurrent therapy: biologic therapy * more than 5 years since prior biologic therapy for cancer chemotherapy * more than 5 years since prior chemotherapy for cancer endocrine therapy * at least 28 days since prior tamoxifen * no prior systemic estrogen modifiers (serms) or aromatase inhibitors * concurrent hormonal contraception (i.e., pills, patches, or shots) allowed provided contraception was initiated prior to study entry radiotherapy * no prior radiotherapy to the breast to be studied surgery * not specified other * at least 7 days since prior anticoagulant therapy * more than 1 month since prior chronic daily aspirin or nonsteroidal anti-inflammatory drugs (nsaids) of more than 7 days duration * concurrent intermittent aspirin or nsaids allowed (no more than 10 days per month) * no concurrent participation in another clinical trial for treatment or prevention of cancer unless no longer receiving treatment and is in the follow-up phase

Keywords: breast cancer breast cancer in situ lobular breast carcinoma in situ ductal breast carcinoma