Comparing Letrozole Given Alone to Letrozole Given With Avastin in Post-Menopausal Women Breast Cancer

Preclinical and clinical data have demonstrated that up-regulation of tumor cell VEGF is an
important mechanism to subvert estrogen dependence in hormone responsive breast cancer
resulting in reduced therapy response or tumor resistance to hormonal therapy; thus, it is
hypothesized that the combination of an anti-VEGF agent (Avastin, an anti-VEGF monoclonal
antibody) and hormonal therapy should be more effective than hormonal therapy alone for the
treatment of breast cancer.

Inclusion Criteria:

All patients must meet the following criteria to be eligible for study entry:

- Pathologically confirmed invasive ductal carcinoma or invasive lobular carcinoma of
the breast, T2-T3 / T4a-c / N0-2 / M0, with positive estrogen and/or progesterone
receptors, and Her-2-neu negative. Patients with inflammatory breast cancer will not
be included (T4d). Patients previously treated patients with no measurable disease or
patients with metastatic disease will be excluded.

- Give written informed consent prior to study specific screening procedures, with the
understanding that the patient has the right to withdraw from the study at any time,
without prejudice.

- Patients must be postmenopausal, defined as one of the following:

- Patients > 50 years of age with no spontaneous menses for at least 12 months,

- Bilateral oophorectomy

- Be ambulatory (outpatient) and have an ECOG PS <1.

- Patients must have measurable disease by mammogram and/or breast ultrasound (in
special cases a dedicated breast MRI may be clinically indicated). The target lesion
must not have been previously irradiated.

- No prior chemotherapy.

- Patients must have adequate organ and marrow function as defined as follows: absolute
neutrophil count > 1,500/mm3, hemoglobin > 8.0 g/dl, platelets > 75,000/mm3, total
bilirubin < 2 mg/dl, serum creatinine < 2 mg/dl, Transaminases (AST, ALT) may be up to
2 x institutional upper limit of normal. In addition < 1 gr of protein in 24 hr urine
collection and urine protein/creatinine ratio < 1.0.

- No life threatening parenchymal disease or rapidly progressing disease warranting
cytotoxic chemotherapy.

- Hypertension must be controlled (<150/100 mmHg).

- Ejection Fraction > 50% by echocardiogram. (LVEF greater than 75% at baseline should
be reviewed and/or the test repeated as it may be falsely elevated).

- No history of thrombosis during the previous 12 months.

Exclusion Criteria:

- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than this sponsor-investigator
Bevacizumab cancer study.

- Uncontrolled high blood pressure (>150/100 mmHg).

- Unstable angina

- New York Heart Association (NYHA) Grade III or greater congestive heart failure

- History of myocardial infarction or unstable angina within 12 months

- History of stroke or TIA within 12 months

- Clinically significant peripheral vascular disease

- History of a bleeding disorder

- Presence of central nervous system or brain metastases

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, anticipation of need for major surgical procedure during the course of
the study

- Minor surgical procedures (excluding fine needle aspirations or core biopsies) within
5 days prior to Day 0

- Pregnant (positive pregnancy test) or lactating

- Urine protein: creatinine ratio greater than or equal to 1.0 at screening or patients
demonstrating > 1 gr of protein in 24 hr urine collection within 4 weeks prior to
study entry will not participate in the trial.

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within 6 months prior to Day 0

- Serious, non-healing wound, ulcer, or bone fracture

- Unwilling or unable to comply with the protocol for the duration of the study.

- Psychiatric illness/social situations that would limit compliance with study
requirements.

- History of another malignancy within the last five years except non-melanoma skin
cancer and carcinoma in-situ of uterine cervix.

- Patients with metastatic disease.