Bevacizumab and Letrozole in Treating Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer That Cannot Be Removed By Surgery

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed carcinoma of the breast

  • Locally advanced or metastatic (stage IV) disease
  • Unresectable disease
• Measurable or nonmeasurable disease

• May have had stable or progressive disease after ≤ 2 prior conventional chemotherapy regimens for treatment of locally advanced or metastatic breast cancer

  • Prior chemotherapy in the adjuvant or metastatic setting is not required
  • Any number of prior neoadjuvant or adjuvant chemotherapy regimens allowed
  • Prior treatment with high-dose chemotherapy and autologous stem cell or bone marrow transplantation is considered 1 regimen when administered for metastatic disease (including induction chemotherapy and preparative regimen)

• May have had stable or responding disease on prior nonsteroidal aromatase inhibitors (e.g., letrozole, anastrozole, or aminogluthemide)

  • Any prior aromatase inhibitor-related toxicity ≥ grade 3 must have resolved ≥ 4 weeks before the start of study treatment
• May have had disease progression on other prior hormonal therapy (e.g., selective estrogen receptor modulators [SERMs], receptor downregulators [SERDs], or ovarian suppression) in the adjuvant or metastatic setting
• No history or evidence of primary brain tumor or brain metastases by CT scan or MRI
• Must have estrogen receptor- and/or progesterone receptor-positive tumor

PATIENT CHARACTERISTICS:

• Rendered postmenopausal with ovarian suppression (ovarian suppression with a depot LH-RH agonist allowed) prior to the start of study treatment OR is already postmenopausal, as defined by 1 of the criteria:

  • No spontaneous menses for ≥ 12 months if the patient is ≥ 50 years old
  • Amenorrheic for ≥ 12 months if the patient is < 50 years old, with serum estradiol and follicle-stimulating hormone (FSH) levels within the institutional postmenopausal range

  • Bilateral oophorectomy

    • At least 28 days since surgical oophorectomy
  • Patients who have had prior hysterectomy but intact ovaries must be ≥ 55 years old, or have serum estradiol and FSH levels within the postmenopausal range
  • Ongoing ovarian suppression with a depot LH-RH agonist
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 3 months
• Female only
• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 75,000/mm^3
• WBC ≥ 2,500/mm^3
• AST and ALT ≤ 2.5 times upper limit of normal
• Bilirubin normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min

• No proteinuria at baseline

  • Patients who unexpectedly have ≥ +1 proteinuria must undergo a 24-hour urine collection that demonstrates ≤ 500 mg of protein over 24 hours
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No presence of bleeding diathesis or coagulopathy
• No history of allergic reaction to compounds of similar chemical or biologic composition to letrozole or bevacizumab
• No serious, nonhealing wound, ulcer, or bone fracture
• No unstable angina pectoris
• No serious cardiac arrhythmia requiring medication
• No uncontrolled hypertension
• No myocardial infarction
• No New York Heart Association class II-IV congestive heart failure
• No peripheral vascular disease ≥ grade II within the past year
• No other clinically significant cardiovascular disease
• No history or evidence of other CNS disease by CT scan or MRI, including seizures not controlled with standard medical therapy or stroke
• No gastrointestinal tract disease resulting in an inability to take oral medication
• No requirement for IV alimentation
• No significant traumatic injury within the past 28 days
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled intercurrent illness

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior steroidal aromatase inhibitors (e.g., exemestane) unless administered in the adjuvant setting (not for metastatic disease) and ≥ 12 months have elapsed since last treatment
• Any number of prior immunotherapies (e.g., trastuzumab [Herceptin^®] or vaccines) in the adjuvant or metastatic setting allowed
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• More than 3 weeks since prior radiotherapy
• More than 3 weeks since prior immunotherapy
• More than 3 weeks since prior investigational therapy
• More than 2 weeks since prior hormonal therapy except letrozole therapy or a luteinizing hormone-releasing hormone (LH-RH) agonist for ovarian suppression
• No prior surgical procedures affecting absorption
• More than 28 days since prior major surgery or open biopsy
• At least 24 hours since prior placement of indwelling catheters

• At least 10 days since prior and no concurrent full-dose oral or parenteral anticoagulants or thrombolytic agents except as required to maintain patency of preexisting, permanent indwelling IV catheters

  • Patients receiving warfarin should have INR < 1.5
• No prior bevacizumab
• No other prior KDR inhibitors (e.g., vascular endothelial growth factor [VEGF] Trap, SU5416, SU6668, ZD6474, vatalanib, AEE788, or IMC-1CII)
• No other concurrent investigational agent
• No concurrent chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function (e.g., cyclooxygenase-1 inhibitors)
• Concurrent bisphosphonates (e.g., zoledronate or pamidronate) or growth factors allowed
• No other concurrent anticancer agents or therapies