Chemotherapy With or Without Bevacizumab in Treating Women With Stage I, Stage II, or Stage IIIA Breast Cancer That Can Be Removed By Surgery

Inclusion Criteria

• •The patient must have consented to participate and must have signed and dated an appropriate Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines for the study treatment and submission of pre-entry core biopsy material for correlative studies.
• •Patients must be female.
• •Patients must be 18 years of age or older.
• •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• •The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy.
• •The primary breast tumor must be palpable and measure greater than or equal to 2.0 cm on physical exam.
• •All patients must have their left ventricular ejection fraction (LVEF) assessed by multigated acquisition (MUGA) scan or echocardiogram within 3 months prior to study entry. The LVEF must be greater than or equal to the lower limit of normal (LLN) for the cardiac imaging facility performing the study. Note: If the cardiac imaging facility cannot provide a LLN, use 50% as the LLN value.
• •\- Note: Since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments to determine if bevacizumab therapy can be continued, it is critical that this baseline study be an accurate assessment of the patient's LVEF. If the baseline LVEF is greater than 75%, the investigator should have the study reviewed for accuracy prior to study entry. Following study entry, the LVEF determination may be reviewed up until the time of the post-chemotherapy (preoperative) evaluation. Please note that if a more accurate value is obtained from the review of the baseline MUGA or echocardiogram, the correct value must be submitted to the NSABP before the post-chemotherapy (preoperative) MUGA or echocardiogram is performed or it cannot be used for managing postoperative bevacizumab.
• •All patients must have an EKG within 3 months prior to study entry.
• •At the time of randomization:
• •* Absolute neutrophil count (ANC) must be greater than or equal to 1200/mm3.
• •* Platelet count must be greater than or equal to 100,000/mm3.
• •* Hemoglobin must be greater than or equal to 10 g/dL.
• •* There must be evidence of adequate hepatic function by these criteria:
• •* Total bilirubin must be less than or equal to the ULN for the lab unless the patient has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN) resulting from Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and
• •* Alkaline phosphatase must be less than or equal 2.5 x ULN for the lab; and
• •* Aspartate Aminotransferase (AST) must be less than or equal to 1.5 x ULN for the lab.
• •* Alkaline phosphatase and AST may not both be greater than the ULN. For example, if the alkaline phosphatase is greater than the ULN but less than or equal 2.5 x ULN, then the AST must be less than or equal the ULN. If the AST is greater than the ULN but less than or equal 1.5 x ULN, then the alkaline phosphatase must be less than or equal ULN.
• •Patients with either skeletal pain or alkaline phosphatase that is greater than ULN but less than or equal 2.5 x ULN are eligible for inclusion in the study if bone scans do not demonstrate metastatic disease. Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy.
• •Patients with AST or alkaline phosphatase greater than ULN are eligible for inclusion in the study if liver imaging does not demonstrate metastatic disease and adequate bone marrow and liver function results as described above are met.
• •The following criteria for evidence of adequate renal function must be met:
• •Serum creatinine less than or equal ULN for the lab.
• •Calculated creatinine clearance must be greater than 50 mL/min.
• •Urine protein/urine creatinine (UPC) ratio must be less than 1.0.
• •Patient must be able to swallow oral medications.
• •Therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer prevention. (Patients are eligible only if these medications are discontinued prior to randomization.)
• •Prior history of breast cancer, including DCIS. (Patients with a history of lobular carcinoma in situ \[LCIS\] are eligible.)
• •Prior therapy with anthracyclines, taxanes, capecitabine, 5-FU (fluorouracil), gemcitabine, or bevacizumab for any malignancy.
• •Cardiac disease that would preclude the use of anthracyclines. This includes:
• •* angina pectoris that requires the use of anti-anginal medication;
• •* history of documented congestive heart failure;
• •* serious cardiac arrhythmia requiring medication;
• •* severe conduction abnormality;
• •* valvular disease with documented cardiac function compromise; and
• •* uncontrolled hypertension defined as BP greater than 150/90 on antihypertensive therapy. (Patients with hypertension that is well controlled on medication are eligible.)
• •History of myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function.
• •History of transient ischemic attack (TIA) or cerebrovascular accident (CVA).
• •History of other arterial thrombotic event within 12 months before study entry.
• •Symptomatic peripheral vascular disease.
• •Any significant non-traumatic bleeding within 6 months before study entry.
• •Serious or non-healing wound, skin ulcers, or incompletely healed bone fracture.
• •Gastroduodenal ulcer(s) determined by endoscopy to be active.
• •Invasive procedures defined as follows:
• •* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to planned start of study therapy. (Note: Placement of a vascular access device is not considered a major surgical procedure.)
• •* Anticipation of need for major surgical procedures (other than the required breast surgery) during the course of the study.
• •Known bleeding diathesis or coagulopathy. (Patients on warfarin with an in-range international normalized ratio \[INR\] \[usually between 2 and 3\] are eligible.)
• •Sensory/motor neuropathy greater than or equal grade 2, as defined by the NCI's Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3.0).
• •Other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude treatment with any of the treatment regimens or would prevent required follow-up.
• •Conditions that would prohibit administration of corticosteroids.
• •History of severe hypersensitivity reaction to drugs formulated with polysorbate 80.
• •Administration of any investigational agents within 30 days before study entry.
• •Pregnancy or lactation at the time of proposed randomization.