INCLUSION CRITERIA:
Postmenopausal female.
Postmenopausal defined as no menses for at least 12 months or bilateral oopherectomy. In unclear cases, (e.g. 50 year old who has had hysterectomy) chemical confirmation of postmenopausal status may be confirmed with FSH greater than 35 U/L.
Elevated risk for developing invasive breast cancer by virtue of one of the following criteria:
Gail Model risk of greater than or equal to 1.7% over 5 years from study entry. (This is the same minimum level of risk required for a subject to be eligible for the recently completed NSABP-P1 tamoxifen breast cancer prevention trial).
Lobular neoplasia.
Atypical ductal hyperplasia.
DCIS (ductal carcinoma in situ) that has been previously treated with mastectomy or lumpectomy and radiation, +/- tamoxifen.
Deleterious mutations in BRCA1 or 2 OR A priori risk assessment of 20% chance or greater of carrying BRCA1/2 gene mutation. The BRCAPRO and Couch model will both be used to asses this risk. If a woman has a 20% risk of carrying a BRCA1/2 mutation by either model, she will meet eligibility criteria.
Subjects should be willing to abstain from use of hormonal therapies (e.g. tamoxifen, hormone replacement therapy, oral contraceptive pills, hormone-containing IUDs.E-string is acceptable) and chronic NSAIDs for the duration of the study (chronic use of NSAIDs is defined as a frequency greater than 3 times/week for more than two weeks per year and includes low dose aspirin). Vitamin E and venlafaxine will be offered as supportive care for women with menopausal symptoms. Acetaminophen will be offered for pain control.
ECOG performance status 0-1.
Subject has been counseled regarding her options and has signed the informed consent document.
Baseline DEXA scan with BMD T-score greater than or equal to 1.5 at AP spine.
Hemoglobin greater than or equal to 11 g/dl.
Creatinine less than 1.5 times the upper limits of normal.
ALT or AST less than 2.5 times upper limit of normal.
No investigational agent for the past 30 days.
If history of cancer (other than invasive breast cancer, squamous or basal cell skin cancers), subject must have no evidence of disease at time of enrollment AND no history of cancer directed treatment in the 2 years preceeding enrollment.
EXCLUSION CRITERIA:
Current or recent chronic use (within 6 months) of hormonal medications, e.g. oral contraceptive pills, hormone replacement therapy, tamoxifen, raloxifene, IUD with progestins or corticosteroids. Subjects on chronic topical or inhaled steroids will not be eligible for the study.
Use of aspirin, NSAIDs, celecoxib or rofecoxib within last 72 hours.
Current use of phenytoin, carbamazepine, rifampin due to increased estrogen metabolism.
Current use of warfarin, fluconazole, lithium due to potential interactions with celecoxib. (If a subject is required to start warfarin after she is enrolled, she will not need to be taken off study).
A history of gastric ulcers, peptic ulcer disease or gastrointestinal bleeding, active GI disease (e.g., inflammatory bowel disease), a chronic or acute renal, hepatic or pancreatic disorder, or any other condition which, in the opinion of the Investigator, might preclude the use of an NSAID (e.g., congestive heart failure).
History of clotting or bleeding disorder.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to exemestane (e.g. anastrozole, letrozole, formestane) or celecoxib (e.g. rofecoxib).
Aspirin sensitive asthma.
Allergy to sulfonamides.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
History of invasive breast cancer.
Warren Grant Magnuson Clinical Center (CC)