Preoperative Window of Endocrine Therapy Provides Information to Increase Compliance

Patients who are eligible (newly diagnosed hormone positive clinical stage 1 or 2 breast
cancer) will be approached about the study. If they sign informed consent a prescription for
21 doses of Tamoxifen will be provided. The patient's surgery will be scheduled at a time
convenient for the patient and the surgeon. Once the surgery has been scheduled, a medication
calendar will be completed that allows the patient to take tamoxifen for 7 days
preoperatively with the 7th dose of tamoxifen to coincide with the day before surgery. The
patient will continue to take tamoxifen for 2 weeks (14 days) after surgery. Patients will
then proceed along normal treatment guidelines. For those needing chemotherapy or radiation
therapy, we recommend the long term endocrine therapy start at the conclusion of chemo and/or
radiation treatments. For those not going on to any additional therapy, the prescription for
endocrine therapy will be written at the initial post-operative visit.

Unstained slides from the formalin-fixed, paraffin-embedded tissue blocks from the patient's
breast tissue from which the original diagnosis of breast cancer was made by H&E will be
stained for Ki67. After endocrine therapy and subsequent resection, carcinoma will be
confirmed by the participating pathologist on H&E, and Ki67 will be performed on unstained
slides from a representative tissue block containing invasive carcinoma. The pathologist will
circle a designated area of tumor on the H&E slide and both the H&E and immunostained (Ki67)
slides will be scanned in a digital imaging device (Aperio XT Scanscope), which
quantitatively analyzes the tumor designated by the pathologist with image analysis
algorithms. The algorithm accurately detects regions of interest and distinguishes cells and
sub-cellular objects within these target regions. It determines morphology and expression
profiles per individual cell or cell compartment. For Ki67 analysis, a nuclear
Immunohistochemistry (IHC) algorithm will be used.

Inclusion Criteria:

- Age > 18 years old

- Diagnosed with hormone receptor positive invasive breast cancer (estrogen receptor
(ER) or progesterone receptor (PR) or both >1%) by core needle biopsy

- Clinical American Joint Committee on Cancer (AJCC) 7th edition Stage 1 or 2

- Candidate for surgical therapy

- Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2

- No chemotherapy or endocrine therapy for breast cancer in last 5 years

- Paraffin fixed core needle tissue block, or biopsy punch available for central
analysis for proliferative markers

- Not pregnant or lactating and practicing adequate birth control if premenopausal

- Able and willing to provide informed consent

Exclusion Criteria:

- Prior personal history of uterine cancer

- Prior personal history of stroke or deep vein thrombosis (DVT)

- Current therapy with strong CYP2D6 inhibitors The following medications should not be
administered with tamoxifen (21 day treatment period) and will need to be stopped for
the designated period of time prior to starting the study tamoxifen.

No other prior malignancy is allowed except for the following: adequately treated basal
cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage 0, I
or II cancer from which the patient is currently in complete remission, or any other cancer
from which the patient has been disease-free for 5 years

Fluoxetine - should be discontinued 30 days prior to starting tamoxifen Paroxetine - should
be discontinued 5 days prior to starting tamoxifen Sertraline - should be discontinued 5
days prior to starting tamoxifen Bupropion - should be discontinued 5 days prior to
starting tamoxifen

- Concurrent coumarin-type anticoagulation therapy

- Any other contraindications to tamoxifen therapy