Anti-Angiogenesis Treatment After Preoperative Chemotherapy: A Pilot Study in Women With Operable Breast Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed invasive breast cancer, preoperative stages
II-III per AJCC 6th edition, based on baseline evaluation by clinical examination
and/or breast imaging

- Patients must have completed preoperative (neoadjuvant) chemotherapy with a standard
chemotherapy regimen. No more chemotherapy should be planned.

- Patients must have completed definitive resection of primary tumor with adequate
excision of gross disease.

- For patients receiving adjuvant radiation therapy, treatment must be completed prior
to initiation of protocol therapy.

- Patients must have the presence of significant residual invasive disease on
pathologic review following their preoperative chemotherapy.

- LVEF > institutional limits of normal after preoperative chemotherapy, as assessed by
ECHO or nuclear medicine gated study, within 30 days prior to initiating
protocol-based treatment.

- ECOG performance status 0-1

Exclusion Criteria:

- Inadequate organ function, as measured by laboratory assessment after preoperative
chemotherapy and within 14 days of beginning protocol-based treatment

- Patients with metastatic disease are ineligible.

- Known HIV infection

- Patients may not be pregnant, expect to become pregnant, plan to conceive a child
while on study, or breastfeeding

- Uncontrolled intercurrent illness

- Non-healing wounds or major surgical procedures (such as breast surgery) other than
that for venous access device or diagnostic study are not permitted within 28 day
prior to enrollment

- History of abdominal fistula, GI perforation, intra-abdominal abscess, or serious,
non-healing wound, ulcer, or bone fracture within 6 months prior to initiating
bevacizumab

- Patients with any history of arterial thromboembolic events, including transient
ischemic attack (TIA), cerebrovascular event (CVA), unstable angina, or myocardial
infarction (MI) within the past 6 months. Patients with clinically significant
peripheral arterial disease should also be excluded

- History of bleeding diathesis or coagulopathy

- History of grade 3 or 4 allergic reactions to compounds of similar chemical or
biologic composition to cyclophosphamide (such as other alkylating agents) or
methotrexate (such as other antimetabolites)

- Prior history of malignancy treated without curative intent, excluding
nonmelanomatous skin cancer

- Patients with large or rapidly accumulating pleural or abdominal effusions

- Current use of anticoagulants is allowed as long as patients have been on a stable
dose for more than two weeks with stable INR

- Chronic therapy with full dose aspirin (< 325 mg/day) or standard non-steroidal
anti-inflammatory agents is allowed

- Patients may not receive other investigational agents while on study