DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed invasive breast cancer

  • Metastatic (stage IV) disease confirmed by histology or cytology, physical exam, or radiologic study

• Measurable disease

  • At least one unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
  • Measurable lesions in a previously irradiated field must have progressed after radiotherapy
• HER2-positive patients must have received prior trastuzumab (Herceptin^®) for advanced disease or in the adjuvant setting
• No evidence of brain metastases by brain CT scan or MRI

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-1 OR
• Karnofsky 70-100%

Life expectancy

• More than 6 months

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 100,000/mm^3
• No bleeding diatheses (including hemoptysis)

Hepatic

• AST and ALT ≤ 4.0 times upper limit of normal (ULN)
• Bilirubin ≤ 2 times ULN

Renal

• Creatinine ≤ 2.0 mg/dL
• Urinary protein < 500 mg/24-hour-urine collection OR
• Protein urinalysis < 1+

Cardiovascular

• LVEF ≥ 50% by echocardiogram or nuclear medicine gated study
• No poorly controlled hypertension
• No prior blood clots
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of grade 3 or 4 allergic reaction to compounds of similar chemical or biological composition to cyclophosphamide or methotrexate
• No concurrent uncontrolled illness
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior experimental angiogenesis inhibitors
• No concurrent filgrastim (G-CSF)
• Concurrent epoetin alfa growth factor support allowed

Chemotherapy

• Prior adjuvant chemotherapy for early-stage breast cancer allowed, including cyclophosphamide-based chemotherapy
• No more than 1 prior chemotherapy regimen for metastatic breast cancer
• No prior oral cyclophosphamide- or methotrexate-based therapy for metastatic disease

Endocrine therapy

• Prior hormonal therapy in the adjuvant or metastatic setting or for early-stage breast cancer allowed
• No concurrent hormonal therapy, including luteinizing hormone-releasing hormone agonists

Radiotherapy

• See Disease Characteristics
• Prior radiotherapy in the metastatic or early-stage setting allowed
• Concurrent radiotherapy allowed

Surgery

• More than 28 days since prior surgery except for venous access device or diagnostic study

Other

• Recovered from prior therapy

• No concurrent anticoagulation or chronic aspirin therapy (> 325 mg/day)

  • Concurrent low-dose anticoagulation or thrombolytic agents for venous access patency allowed
• No other concurrent investigational or experimental therapy
• No other concurrent anticancer agents or therapies

• Concurrent bisphosphonates allowed provided skeletal sites are not the primary sites used in assessing response

  • If skeletal sites are being followed for measurable response, bisphosphonates must be initiated at least 4 weeks before study entry