The investigators hypothesize that the combination of Gemzar®, Abraxane® and Avastin will increase the progression-free survival (PFS) in patients with first line metastatic breast cancer and in patients who received neoadjuvant and/or adjuvant chemotherapy present with definable metastatic disease, 6 or more months after primary treatment.

This is a phase 2, single arm study. Participants will be treated with combination Gemzar, Abraxane and Avastin therapy until disease progression. Each treatment cycle is 28 days.

Inclusion Criteria

1. Patients must either be:

   • treatment-naïve with newly diagnosed her2neu non-overexpressing (non amplified) metastatic (Stage IV) breast cancer, or
   • HER2/neu-negative patients with metastasis diagnosed 6 or more months after completing primary systemic treatment (neoadjuvant, adjuvant chemotherapy).

2. No previous chemotherapy regimen for metastatic breast cancer.

3. 18 years of age or older.

4. Measurable disease as defined by RECIST criteria or evaluable disease.

5. Eastern Cooperative Oncology Group (ECOG) 0-1.

6. Life expectancy greater than 3 months.

7. For female (or male) patients, either pre- or post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control for the duration of the study

8. Provide written informed consent before any study-related procedure not part of normal medical care is conducted

9. Willing and able to comply with the protocol requirement

10. Laboratory parameters as follows:

    • Neutrophils: 1.5 x109/L or greater
    • Platelets: 100 x109/L or greater
    • Hemoglobin: ≥ 9.0 g/dL
    • Serum Creatinine: ≤ 1.5mg/dL
    • Bilirubin: ≤ ULN, except when caused by metastatic disease
    • Alanine transaminase (ALT)/Aspartate transaminase (AST): ≤ 2.5 times the upper limit of the normal range (ULN) except when caused by metastatic disease
    • Urine protein creatinine (UPC) ratio < 1.0 at screening.

Exclusion Criteria

1. Previous treatment with gemcitabine.
2. History of Gastrointestinal Bleeding in the previous 3 months.
3. Chemotherapy within 4 weeks prior to enrollment.
4. Radiation therapy or evidence of acute effects of radiation therapy within 2 weeks prior to enrollment.
5. Any major surgery within 4 weeks prior to enrollment.
6. Presence of central nervous system or brain metastases.
7. Urine protein: creatinine ratio ≥ 1.0 at screening.
8. Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications).
9. A prior history of hypertensive crisis or hypertensive encephalopathy.
10. Peripheral neuropathy > grade I.
11. Clinical AIDS or known positive HIV serology
12. No concurrent clinically evident malignancy is allowed except inactive non-melanoma skin cancer and inactive cervical cancer diagnosed or other cancer for which the patient has been disease-free for five years.
13. Unstable angina.
14. New York Heart Association (NYHA) Grade II or greater congestive heart failure
15. History of myocardial infarction within 6 months.
16. History of stroke within 6 months.
17. Clinically significant peripheral vascular disease.
18. Evidence of bleeding diathesis or coagulopathy
19. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment, anticipation of need for major surgical procedure during the course of the study.
20. Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to enrollment.
21. Pregnant (positive pregnancy test) or lactating.
22. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment
23. Serious, non-healing wound, ulcer, or bone fracture
24. Inability to comply with study and/or follow-up procedures
25. Participants with serious medical or psychiatric illness that would render chemotherapy unsafe are ineligible.
26. Participants cannot have been in another experimental drug study other than a Bevacizumab cancer study within 4 weeks of the first infusion of these study medications.