Sorafenib and Fulvestrant in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Aromatase Inhibitor Therapy

DISEASE CHARACTERISTICS:

• Diagnosis of incurable breast cancer

  • Locally advanced or metastatic disease

• Measurable or evaluable disease

  • Measurable disease is defined as ≥ 1 uni-dimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral computed tomography(CT) scan

    • Bone-only metastases that can be imaged with bone scan AND magnetic resonance imaging (MRI) or bone scan AND plain x-ray is considered measurable disease
    • Tumor lesions that are situated in a previously irradiated area are considered measurable only if they are progressing at the time of study entry

  • Evaluable disease includes unresectable skin/chest wall metastases that can be photographed and whose size can be measured with a ruler

    • Bone-only metastases that can only be imaged using bone scan or malignant pleural effusion(s) only are not considered evaluable disease

• Previously treated with a third-generation aromatase inhibitor (e.g., letrozole, anastrazole, or exemestane) AND meets one of the following criteria:

  • Progressed during palliative aromatase inhibitor therapy
  • Recurred during adjuvant aromatase inhibitor therapy
  • Recurred within 12 months of completing adjuvant aromatase inhibitor therapy

• Human Epidermal growth factor Receptor 2(HER2/neu)-negative tumor

  • No Human Epidermal growth factor Receptor 2(HER2/neu) overexpression (i.e., tumor staining 3+ by immunohistochemistry [IHC] or gene amplified by Fluorescence In Situ Hybridization [FISH])

• Hormone receptor status:

  • Estrogen receptor and/or progesterone receptor positive, defined as ≥ 10% of malignant cells with positive nuclear staining

PATIENT CHARACTERISTICS:

• Postmenopausal
• Eastern Cooperative Group(ECOG) performance status 0-1
• Life expectancy ≥ 16 weeks
• Neutrophil count ≥ 1,500/mm^³
• Platelet count ≥ 100,000/mm^³
• Hemoglobin ≥ 9.0 g/dL
• Creatinine < 2 mg/dL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase(AST) ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)
• International Normalized Ratio(INR) < 1.5 OR Prothrombin time/ partial thromboplastin time (PT/PTT) normal
• Left ventricular ejection fraction(LVEF) normal by Multiple Gated Acquisition(MUGA) or ECHO
• No known allergy to sorafenib tosylate or fulvestrant

• No cardiac disease, including any of the following:

  • New York Heart Association(NYHA) class III-IV congestive heart failure
  • Unstable angina (anginal symptoms at rest) or new-onset angina (within the past 3 months)
  • Myocardial infarction within the past 6 months
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• No uncontrolled hypertension, defined as systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg despite optimal medical management
• No thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attacks), within the past 6 months
• No known HIV infection or chronic hepatitis B or C infection
• No infection that requires IV antibiotics or produces a fever > 100°F within the past 72 hours
• No pulmonary hemorrhage/bleeding event ≥ Common terminology criteria for adverse events(CTCAE) grade 2 within the past 4 weeks
• No other hemorrhage/bleeding event ≥ CTCAE grade 3 within the past 4 weeks
• No evidence or history of bleeding diathesis or coagulopathy
• No significant traumatic injury within the past 2 weeks
• No serious, nonhealing wound, ulcer, or bone fracture
• No condition that impairs the patient's ability to swallow whole pills
• No malabsorption problem
• No second malignancy within the past 5 years, except adequately treated and cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No underlying medical condition that, in the principal investigator's opinion, will make the administration of study drug hazardous or would obscure the interpretation of adverse events

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior chemotherapy for metastatic or unresectable locally advanced breast cancer
• No prior sorafenib tosylate or other Vascular endothelial growth factor(VEGF)-targeting therapies
• More than 2 weeks since prior major surgery or open biopsy
• No concurrent anticoagulation with warfarin or heparin
• No concurrent Hypericum perforatum (St. John wort) or rifampin
• No other concurrent anticancer agents, including chemotherapy or biological therapy
• No other concurrent investigational drugs
• Concurrent bisphosphonates allowed