S0300, Celecoxib in Preventing Breast Cancer in Premenopausal Women

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.

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