Trial Using Docetaxel Cytoxan in Breast Cancers With High Recurrence Scores

Previous studies have shown that chemotherapy has the same effect on treating breast cancer
whether you receive it before or after surgery. Receiving chemotherapy before surgery,
rather than after surgery, may allow you to have less extensive surgery by shrinking the
size of your cancer. The purpose of this study is to assess if docetaxel and cytoxan can
shrink the size of your breast tumor and allow you to preserve your breast or have less
extensive surgery on your breast. Additionally, by receiving chemotherapy before surgery, we
will be able to determine if your cancer is responsive to chemotherapy. Prior to entering
this study, a special test, called the Oncotype DX assay, will be performed on a small
amount of your cancer from the biopsy you had at the time you were diagnosed with breast
cancer, to determine the likelihood that your cancer will benefit from and shrink with
chemotherapy. You will only be eligible to enter this study if the recurrence score
determined using the Oncotype DX assay is 25 or greater. Patients with hormone
receptor-positive breast cancers with recurrence scores greater than or equal to 25 have
been previously demonstrated to obtain a significant benefit from chemotherapy given after
surgery.

In addition, researchers would like to examine proteins present in your blood and proteins
present in your breast tissue. These additional parts of the study are voluntary and are NOT
required to participate in this study.

Inclusion Criteria:

- Signed informed consent.

- Histologically or cytologically confirmed breast carcinoma.

- Early stage breast cancer (T1c-3, cN0-3, cM0).

- No evidence of disease outside the breast or chest wall, except ipsilateral axillary
or internal mammary lymph nodes.

- Pre-treatment biopsy with the following characteristics:

- Hormone receptor-positive cancer as defined as ER and/or progesterone receptor
(PR)-positive by standard immunohistochemistry (IHC)

- HER2-negative (HER2 ≤ 2 by IHC; if HER2 2+ by IHC must be FISH non-amplified)

- Recurrence score ≥ 25 using Oncotype DX 21-gene assay

- Patients must have measurable disease as defined by palpable lesion with both
diameters ≥ 1cm measurable with caliper or a positive mammogram or ultrasound with at
least one dimension ≥ 1cm. Baseline measurements of the indicator lesions must be
recorded on the Patient Registration Form. To be valid for baseline, the measurements
must have been made within the 14 days if palpable. If not palpable, a mammogram or
MRI must be done within 14 days. If palpable, a mammogram or MRI must be done within
2 months prior to study entry. If clinically indicated, xrays and scans must be done
within 28 days of study entry.

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

- No prior chemotherapy, hormonal therapy, biologic therapy or radiation therapy for
breast cancer.

- Adequate organ function within 14 days of study entry:

- Bone marrow function: absolute neutrophil count (ANC) ≥ 1500/mm³, Hgb > 8.0
g/dl, and platelet count ≥ 100,000/mm³.

- Hepatic function: total bilirubin < upper limit of normal (ULN). Serum glutamic
oxaloacetic transaminase (SGOT)(AST) or serum glutamic pyruvic transaminase
(SGPT)(ALT) and alkaline phosphatase ≤ 1.5 x ULN.

- Renal function: calculated creatinine clearance (CrCl) ≥ 30 mL/min using the
Cockroft Gault equation.

- Patients must be at least 18 years of age.

Exclusion Criteria:

- Pregnant or lactating women are not eligible. Women of childbearing potential must
have a negative serum pregnancy test completed within 7 days of study entry, and use
an appropriate form of birth control throughout the trial period.

- No medical, psychological or surgical condition which the investigator feels might
compromise study participation.

- No patients with history within the last 5 years of previous or current malignancy at
other sites with the exception of adequately treated carcinoma in-situ of the cervix
or basal or squamous cell carcinoma of the skin. Patients with a history of other
malignancies who remain disease free for greater than five years are eligible.

- No evidence of peripheral or sensory neuropathy.

- Patients with a history of severe hypersensitivity reaction to docetaxel or other
drugs formulated with polysorbate 80 are excluded from participation.

- No serious, uncontrolled, concurrent infection(s).

- No clinically significant cardiac disease (e.g. congestive heart failure, symptomatic
coronary artery disease and cardiac arrhythmias not well controlled with medication)
or myocardial infarction within the last 12 months prior to study entry.

- No major surgery within 28 days of study entry.

- No evidence of central nervous system (CNS) metastases.