Patient description: The patient is a 42 year-old postmenopausal woman who had a screening sonogram which revealed an abnormality in the right breast. She had no palpable masses on breast exam. Core biopsy was done and revealed a 1.8 cm infiltrating ductal breast carcinoma in the left upper outer quadrant. Lumpectomy was done and the surgical margins were clear. The tumor was HER2-positive and ER/PR negative. Axillary sampling revealed 1 positive lymph node out of 12 sampled. CXR was unremarkable. She is using “well women” multivitamins daily and no other medication. She smokes frequently and consumes alcohol occasionally. She is in a relation with only one partner and has a history of 3 pregnancies and live births. She breastfed all three children.

Clinical trial eligibility criteria: eligible ages (years): 0.0-999.0,  Breast Neoplasms Postmenopausal female. Postmenopausal defined as no menses for at least 12 months or bilateral oophorectomy. In unclear cases, (e.g. 50 year old who has had hysterectomy) chemical confirmation of postmenopausal status may be confirmed with follicle stimulating hormone (FSH) greater than 35 U/L. Elevated risk for developing invasive breast cancer by virtue of one of the following 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 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 criteria. Prior stage I or II breast cancer at least 2 years out from treatment for invasive disease and no prior use of aromatase inhibitors. Subjects should be willing to abstain from use of hormonal therapies (e.g. tamoxifen, hormone replacement therapy, oral contraceptive pills, hormone-containing intrauterine devices (IUDs). E-string is acceptable). Venlafaxine will be offered as supportive care for women with menopausal symptoms. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Subject has been counseled regarding her options and has signed the informed consent document. Baseline dual-emission x-ray absorptiometry (DEXA) scan with bone mineral density (BMD) T-score greater than or equal to 2.5 at antero posterior (AP) spine. Hemoglobin greater than or equal to 11 g/dl. Creatinine less than 1.5 times the upper limits of normal. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 2.5 times upper limit of normal. No investigational agent for the past 30 days. If history of cancer (other than 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 preceding enrollment  Current or recent chronic use (within 3 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 be eligible for the study.) Current use of phenytoin, carbamazepine, rifampin due to increased estrogen metabolism. 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). 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