Preoperative Cisplatin and Bevacizumab in ER-, PR-, HER2 Negative Breast Cancer

• To prepare for surgery, a small "clip" will be placed into the tumor area so that the surgeon can locate the site of the tumor at the time of surgery. This is a standard procedure for breast cancer.
• The study drugs will be given in four 3-week cycles (about 3 months). Participants will come into the clinic each day they receive study treatment intravenously. Cisplatin will be given on day one of the treatment cycle (once every 3 weeks) for four cycles. Bevacizumab will be given on day one of the treatment cycle for three cycles.
• On day one of each 3-week cycle a physical exam, routine blood tests and urine test will be performed. 7-8 days after chemotherapy, blood tests and a hearing test will be performed. A preoperative study visit will take place 7-10 days before surgery and a physical exam, routine blood tests, Electrocardiogram (EKG) and an Magnetic Resonance Imaging (MRI) of the breast will be performed.
• Surgery to remove the tumor will occur at least three weeks after the last dose of cisplatin and is considered standard of care.
• Postoperative chemotherapy will begin at least three weeks after surgery. Everyone on the research study will receive four 2-week cycles of doxorubicin and cyclophosphamide plus bevacizumab. After the 8 weeks, the doctor will decide which of the following two treatment regimens the participant will receive: Bevacizumab for four 2-week cycles (once every two weeks) or; Paclitaxel plus bevacizumab for four 2-week cycles (once every two weeks).
• At the end of the postoperative chemotherapy, the participant will return to the clinic for a medical history, physical exam, vital signs, performance status, routine blood tests, multiple gated acquisition scan (MUGA) or Echocardiogram Scans, and a hearing test.

Inclusion criteria

• All tumors must be ER-, PR- and HER2-negative
• Clinical stage T2 or T3, N0-3, M0. Subjects with inflammatory breast cancer are not eligible
• For subjects with clinically negative axilla, a sentinel lymph node biopsy will be performed either up front or after preoperative therapy at the discretion of the subject's physicians; for subjects with a clinically positive axilla, a needle aspiration or core biopsy will be performed to confirm the presence of metastatic disease in the lymph nodes.
• 18 years of age or older
• Performance status (PS) of 0 or 1
• Use of an effective means of contraception in subjects of child-bearing potential
• Normal organ function as described in the protocol

Exclusion criteria

• Any prior cytotoxic chemotherapy or radiation for the current breast cancer
• HER2-negative ipsilateral breast recurrence, unless prior treatment consisted of excision alone for ductal carcinoma in situ (DCIS)or breast-conserving treatment and hormonal therapy for DCIS or invasive cancer
• Life expectancy of less than 12 weeks
• Current, recent, or planned participation in an experimental durg study other than a Genentech-sponsored bevacizumab cancer study
• Renal dysfunction for which exposure to cisplatin would require dose modifications
• Steroid dependent asthma
• Peripheral neuropathy of any etiology that exceeds grade 1
• Uncontrolled diabetes
• History of malignancy treated without curative intent
• Any other pre-existing medical condition that would represent toxicity in excess of grade 1
• Inadequately controlled hypertension
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive hear failure
• History of myocardial infarction or unstable angina within 12 months prior to study enrollment
• Any history of stroke or transient ischemic attack at any time
• Known central nervous system (CNS) disease
• Significant vascular disease
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Major surgical procedure, open biopsy, or significant traumatic injury within 21 days prior to study enrollment
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study enrollment
• Serious, non-healing wound, ulcer or bone fracture
• Proteinuria at screening
• Known hypersensitivity to any component of bevacizumab
• Pregnant or lactating