A Pilot Study of Adjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel Plus Sorafenib in Women With Node Positive or High-Risk Early Stage Breast Cancer

Inclusion Criteria:

- Patients must have histologically-confirmed breast cancer with an interval between
definitive surgery that includes axillary lymph node involvement assessment and
initiation of study treatment of less than or equal to 84 days.

- Definitive surgery - either mastectomy with axillary node involvement assessment, or
breast conserving surgery with axillary node assessment. Margins of resected
specimen must be free of invasive disease and/or ductal carcinoma in situ (DCIS).

- Stage I, II, IIIA, and IIIC (T1-3, N3a only). Patients must be either lymph node
positive or high-risk node negative.

- Age > 18 years.

- ECOG performance status 0 or 1.

- Normal cardiac function must be confirmed by left ventricular ejection fraction
(LVEF) by Echocardiography or MUGA scan and electrocardiogram (ECG) within 35 days
prior to initiation of study treatment.

- Patients must have adequate bone marrow function

- Patients must have normal liver function (

- Serum creatinine <= 2mg/dl

- INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation
treatment with an agent such as warfarin or heparin may be allowed to participate.
For patients on warfarin, the INR should be measured prior to initiation of sorafenib
and monitored.

Exclusion Criteria:

- Prior systemic anticancer therapy for breast cancer (immunotherapy, chemotherapy,
hormonal therapy).

- Patients with HER2 positive breast cancer as determined by FISH or IHC3+ standing are
ineligible for this trial.

- Prior anthracycline or taxane therapy.

- Prior radiation therapy for breast cancer.

- Bilateral invasive disease.

- Pre-existing motor or sensory neurotoxicity of a severity ≥ 2 by NCI CTCAE v 3.0
criteria.

- Cardiac disease that includes: myocardial infarction; angina, congestive heart
failure, arrhythmia; valvular heart disease; cardiomegaly on chest imaging or
ventricular hypertrophy on ECG - unless the LVEF is within normal range for the
institution; patients with poorly controlled hypertension (defined as systolic blood
pressure > 150 and /or diastolic blood pressure > 100 mmHg on antihypertensive
medications); patients who receive medications for angina, arrhythmias, or congestive
heart failure.

- Current therapy with raloxifene, tamoxifen or other selective estrogen receptor
modulator

- Concurrent treatment with ovarian hormonal replacement therapy.

- History of prior malignancy within 5 years with the exception of skin cancer or
cervical carcinoma in situ.

- Women who are pregnant (positive pregnancy test) or breast feeding. Subjects of
childbearing potential must use effective birth control measures during treatment.

- Treatment with a non-approved or investigational drug within 30 days before day 1 of
trial treatment.

- Patients with neurological symptoms must undergo a CT scan/MRI of the brain to
exclude brain metastasis.

- Thrombotic or embolic events such as a stroke and transient ischemic attack within
the past 6 months.

- Pulmonary hemorrhage/bleeding event ≥ NCI CTCAE v3.0 Grade 2 within 4 weeks of first
dose of study drug.

- Any other hemorrhage/bleeding event ≥ NCI CTCAE v3.0 Grade 3 within 4 weeks of first
dose of study drug.