Statement: Patients with any of the following conditions will be excluded from the primary trial; grade 1 infection, unstable angina or a grade 4 hemorrhage within the last month.
Primary_evidence: Inclusion Criteria:   Age  18 years.   Histologically or cytologically confirmed breast cancer diagnosis   with metastatic disease. Patients without pathologic or cytologic   confirmation of metastatic disease should have unequivocal   evidence of metastasis.   3. Measurable disease, as per RECIST criteria (Therasse et al.   2000). Measurable disease cannot be previously irradiated   unless progression was documented. Measurable disease is   defined as: at least one lesion that can be accurately measured in   at least one dimension [longest diameter to be recorded] as   >20 mm with conventional techniques, or as >10 mm with spiral   computed tomography (CT) scan. Disease must be measurable,   i.e., bone-only disease or evaluable-only disease is not eligible.   4. Patients with brain metastasis may participate if they:  have undergone appropriate treatment,   are at least 1 month post-treatment,   have no neurologic symptoms,   are not on steroids,   have a follow-up magnetic resonance imaging (MRI) scan that   demonstrates no residual active lesions, and   have no new untreated lesions.   5 The following prior therapies are allowed:   No prior chemotherapy in the metastatic setting. However,   patients must have received prior adjuvant or neo-adjuvant   chemotherapy.   Prior radiation therapy in either the metastatic or early-stage   setting, as long as <25% of the bone marrow has been   treated. Radiation therapy must be completed at least   14 days prior to study registration, and all radiation-related   toxicities must be resolved to  grade 1 before the patient is   eligible for study inclusion.   Any number of hormonal therapies in the neo-adjuvant,   adjuvant, or metastatic setting is allowed. Patients must   discontinue hormonal therapy at least 1 week prior to starting   study treatment. Prior bevacizumab administered >4 weeks before initiation of   study treatment is allowed.   6 HER2-negative status. Documentation of HER2 results must be   available at the time of study enrollment. HER2-negative is   defined as:   Immunohistochemical (IHC) 0 or IHC 1+ OR   Fluorescence in situ hybridization (FISH) negative (defined by   FISH ratio <2.2) OR   Silver in-situ hybridization (SISH) negative (defined by SISH   ratio <2.2).   Patients with an IHC 2+ will need to be validated as HER2-negative   by FISH.   7 An Eastern Cooperative Oncology Group (ECOG) performance   status of < or = to 2.   8. Normal bone marrow function as defined by:   absolute neutrophil count (ANC) >1,500/μL;   platelets >100,000/μL;   hemoglobin >9 g/dL.   9 Normal hepatic function as defined by:   total bilirubin within normal institutional limits;   aspartate aminotransferase (AST) and alanine   aminotransferase (ALT) <2.5 × the institutional upper limit of   normal (ULN) for patients without liver metastasis; <5.0 × ULN   for patients with liver metastasis.   10. Normal renal function as defined by creatinine <1.5 × ULN.   11. Left ventricular ejection fraction (LVEF) within institutional limits of   normal.   12. International normalized ratio (INR) <1.5 or a prothrombin   time/partial thromboplastin time (PT/PTT) within normal limits.   Patients receiving anti-coagulation treatment with an agent such   as warfarin or heparin may be allowed to participate. The INR   should be measured prior to initiation of sorafenib, and for   patients on warfarin, INR should be monitored at least weekly   following initiation of protocol treatment, until the INR is stable and   therapeutic.   13. Life expectancy of >6 months.   14. For women of childbearing potential, negative serum pregnancy   test within 7 days prior to starting treatment.   15. For women of childbearing potential and men, agreement to use a   method of contraception that is acceptable to their physician from   time of first signing the informed consent and for the study   duration. Men should use adequate birth control for at least three   months after the last administration of sorafenib. If a woman   becomes pregnant or suspects she is pregnant while participating   in this study, she must agree to inform her treating physician   immediately. As applicable, patients must agree to discontinue   breast-feeding until at least 3 weeks after their last dose of study   drug.   16. Recovery to < grade 1 toxicity due to prior therapy.   17. Ability to understand and willingness to sign a written informed   consent document.   Exclusion Criteria   More than one (>1) prior chemotherapy regimen.   Treatment with chemotherapy, biologic agents, or targeted agents   within the previous 4 weeks.   Previous treatment with sorafenib or ixabepilone.   Women who are pregnant or breastfeeding.   Neuropathy (motor or sensory) greater than grade 1.   Uncontrolled intercurrent illness including (but not limited to)   ongoing or active infection >grade 2.   Known history of human immunodeficiency virus (HIV), Hepatitis   B, or Hepatitis C infection.   History of other non-breast cancer malignancy treated with   curative intent within the 5 years preceding study enrollment with   the exception of carcinoma in situ of the cervix, non-melanoma   skin cancer, or follicular thyroid cancer.   Concurrent hormonal therapy, chemotherapy other than   ixabepilone, or radiation treatments while on study as well as   treatment with other investigational agents while on study.   Cardiac disease: Congestive heart failure (CHF) greater than New York Heart Association   (NYHA) Class II (see Appendix B).   Unstable angina (anginal symptoms at rest) or new onset angina   (i.e., began within the last 3 months).   Myocardial infarction within the past 6 months.   Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.   Uncontrolled hypertension (systolic blood pressure >150 mmHg   or diastolic pressure >100 mmHg despite optimal medical   management).   Thrombolic or embolic events such as cerebrovascular accident,   including transient ischemic attacks, within the past 6 months.   Pulmonary hemorrhage or bleeding event  grade 2 within   4 weeks of the first dose of study treatment, or any other   hemorrhage or bleeding event  grade 3 within 4 weeks of the   first dose of study treatment.   14. Serious non-healing wound, ulcer, or bone fracture.   15. Evidence or history of bleeding diathesis or coagulopathy.   16. Major surgery, open biopsy or significant traumatic injury within   4 weeks of the first dose of study drugs or anticipation of the need   for major surgical procedure.   17. Chronic use of CYP3A4 inducers and use of the following strong   CYP3A4 inhibitors: ketoconazole, itraconazole, clarithromycin,   atazanavir, nefazodone, saquinavir, telithromycin, ritonavir,   amprenavir, indinavir, nelfinavir, delavirdine, and voriconazole.   Use of these agents should be discontinued at least 72 hours   prior to initiation of study treatment.   18. Use of St. John's Wort or rifampin (rifampicin).   19. Any condition that impairs patient's ability to swallow whole pills or   gastrointestinal (GI) tract disease that involves an inability to take   oral medication, malabsorption syndrome, a requirement for   intravenous (IV) alimentation, prior surgical procedures affecting   absorption, or uncontrolled inflammatory GI disease (e.g., Crohn's   disease or ulcerative colitis).   20. Psychiatric illness/social situations that would limit compliance   with study requirements.   21. Known or suspected allergy to sorafenib, Cremophor EL   (polyoxyethylated castor oil) or a drug formulated in   Cremophor EL such as paclitaxel or any other agent given in the   course of this trial. Exclusion Criteria: