Sorafenib and Anastrozole in Treating Postmenopausal Women With Metastatic Breast Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed breast cancer
• Metastatic disease

• Measurable disease, defined as >=1 unidimensionally measurable lesion, including >= 1 of the following:

  • Lesion >= 10 mm on CT scan (5 mm sections)
  • Lesion >= 20 mm on CT scan or MRI (10 mm sections)
  • Bone disease that is >= 10 mm on MRI
  • Lytic bone lesions that are >= 10 mm on CT scan (with 5 mm sections) OR >= 20 mm on plain film or CT scan (with 10 mm sections)
  • Lesion >= 10 mm on physical exam
• Patients must have received >= 1 prior aromatase inhibitor in either the adjuvant or metastatic setting and must have had either disease recurrence or disease progression on a prior aromatase inhibitor therapy
• No brain metastases diagnosed within the past 6 months OR previously untreated brain metastases
• Estrogen receptor-positive and/or progesterone receptor-positive, defined as > 1% staining by immunohistochemistry or > 10 fmol/mg of protein by radio-ligand dextran-coated steroid binding assay

• Postmenopausal, as defined by 1 of the following:

  • Prior bilateral oophorectomy
  • No menses for >= 12 months in patients with an intact uterus
  • Follicle-stimulating hormone (FSH) in postmenopausal range in patients < 60 years of age who have had a prior hysterectomy or have been amenorrheic for >= 3 months
  • Age >= 60 years
  • Pre- or perimenopausal patients receiving monthly injections of goserelin at a dose of 3.6 mg are eligible
• ECOG 0-2
• More than 3 months
• Absolute neutrophil count >= 1,500/mm3 Platelet count >= 100,000/mm3 No bleeding diathesis
• Bilirubin =< 1.5 times upper limit of normal (ULN AST and ALT =< 2.5 times ULN
• Systolic blood pressure (BP) < 150 mm Hg and diastolic BP < 100 mm Hg on at least one reading prior to study entry No uncontrolled hypertension

• None of the following within the past 6 months:

  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Myocardial infarction
  • Cardiac arrhythmia with hemodynamic compromise
• Not pregnant or nursing
• Able to swallow oral medication
• No known HIV positivity
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other active invasive malignancy within the past 5 years except nonmelanoma skin cancer or treated carcinoma in situ of the cervix
• No other uncontrolled illness
• More than 4 weeks since prior chemotherapy
• No more than 2 prior chemotherapy regimens for metastatic disease
• At least 8 weeks since prior anastrozole therapy
• Concurrent steroids allowed if dose is stable
• More than 4 weeks since prior radiotherapy
• More than 4 weeks since prior major surgery
• Recovered from prior therapy
• No prior sorafenib
• No concurrent therapeutic anticoagulation
• Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial access devices allowed provided PT and PTT are =< 1.5 times ULN

• No concurrent agents that may interact with sorafenib, including any of the following:

  • Hypericum perforatum (St. John's wort)
  • Rifampin
  • P450 CYP3A4 enzyme-inducing anticonvulsants (e.g., phenytoin, carbamazepine, or phenobarbital)
• No other concurrent investigational agents

Exclusion Criteria:

• estrogen receptor status unknown
• history of myocardial infarction within 6 months
• performance status 3
• performance status 4
• premenopausal
• progesterone receptor status unknown
• HIV positive