Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

PRIMARY OBJECTIVES:

I. Non-inferiority of percent change in time of serum estradiol levels, adjusted for baseline
levels, following four up to six weeks of exemestane 25 mg given three times per week or one
time per week compared with exemestane 25 mg daily dosing.

SECONDARY OBJECTIVES:

I. To assess safety and toxicity. II. To support the preventive activity of exemestane we
will investigate the change in Ki-67 and progesterone receptor (PgR) levels in tumor cells
and the adjacent intraepithelial neoplasia or benign histologic structures.

III. To assess possible association of estradiol level with tissue and circulating
biomarkers.

IV. To investigate possible pharmacogenetic markers. V. To assess drug levels on tissue
samples. VI. To investigate tissue and circulating proteomics profiling.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive exemestane orally (PO) once daily (QD) on days 1-7.

ARM II: Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo
PO QD on days 2, 4, 6, and 7.

ARM III: Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7.

In all arms, courses repeat every 7 days for 4-6 weeks in the absence of disease progression
or unacceptable toxicity. Patients then undergo surgery on days 29, 36, or 43.

After completion of study treatment, patients are followed up at 20-30 days.

Inclusion Criteria:

- Postmenopausal women (postmenopausal: age >= 60 years, or amenorrhea >= 12 months, or
bilateral oophorectomy, or - in women with hysterectomy only - follicle stimulating
hormone [FSH] in the menopausal levels as per local institutional guidelines if < 60
years old) with histologically-confirmed estrogen receptor (ER)-positive (>= 10%)
primary breast cancer stage cT0-2, cN0-1, Mx; women with larger tumors who refuse
chemotherapy (chemo) and/or endocrine neoadjuvant therapy can be eligible

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

- Leukocytes >= 3,000/microliter

- Absolute neutrophil count >= 1,500/microliter

- Platelets >= 100,000/microliter

- Total bilirubin =< 2 x institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 1.5 x institutional ULN

- Serum creatinine =< 1.5 times institutional ULN

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Body mass index (BMI) < 18.5 Kg/m^2

- Previous treatment for breast cancer including chemotherapy, endocrine therapy and
radiotherapy; women with prior ductal breast carcinoma in situ (DCIS) who were treated
with surgery only and whose treatment ended >= 2 years prior to enrollment are
eligible for the trial

- Women who are planned to receive neoadjuvant therapy

- Participants may not be receiving investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to exemestane

- 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

- Other co-existing invasive malignancies (with the exclusion of basal cell carcinoma or
skin squamous cell carcinoma) diagnosed during the last 2 years before randomization

- History of severe osteoporosis (T score =< -4 either spine or hip), or presence of
vertebral fracture

- Use of systemic hormone replacement therapy (HRT) in the last 30 days prior to the
randomization; the use of non-systemic estrogen (such as vaginal estrogen use) is
allowed

- Use of any chemopreventive agents (selective estrogen receptor modulators [SERM]) in
the last 3 months

- Concomitant use of CYP3A4 inducer medication (rifampicin, phenytoin, carbamazepine,
phenobarbital, and St. John's wort)