DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic adenocarcinoma of the breast

  • Histologically documented primary breast cancer or biopsy of metastatic site demonstrating HER2/neu gene amplification by fluorescence in situ hybridization, as evidence by 1 of the following:

    • More than 10 HER2 signals/cell uncorrected
    • More than 2 signals/cell corrected for chromosome 17 polysomy (using the PathVysion HER2/neu amplification kit)
• Tumor blocks available for determination of epidermal growth factor receptor expression

• Bidimensionally measurable disease

  • At least 2 cm by conventional radiography or physical examination OR at least 1 cm by spiral CT scan
  • Disease that is assessable but not bidimensionally measurable is allowed in phase I patients only (closed to accrual as of 01/2004)
• No pleural effusions as the sole manifestation of metastatic disease (phase I [closed to accural as of 01/2004] and II patients)
• No bone metastases as the sole manifestation of metastatic disease (phase II patients only)
• No liver metastases occupying more than 30% of the hepatic parenchyma

• No symptomatic or untreated brain metastases unless both of the following are true:

  • Neurologically stable
  • At least 4 weeks since prior corticosteroids

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Granulocyte count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater 9 g/dL (transfusion allowed)
• No hemorrhagic diathesis or active bleeding disorder

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• AST and ALT less than 2.5 times ULN (5 times ULN if due to liver metastases)
• Albumin greater than 3.0 g/dL
• INR no greater than 4 for patients receiving warfarin

Renal:

• Creatinine less than 1.5 times ULN OR
• Creatinine clearance greater than 60 mL/min
• No 2+ or greater proteinuria
• No uncontrolled hypercalcemia (no greater than 11.5 mg/dL)

Cardiovascular:

• Cardiac ejection fraction at least lower limit of normal by MUGA or echocardiogram
• No uncontrolled hypertension
• No unstable angina
• No congestive heart failure
• No myocardial infarction within the past 6 months
• No serious cardiac arrhythmia requiring medication

Pulmonary:

• Phase I patients (closed to accrual as of 01/2004):

  • No prior serious pulmonary events after treatment with trastuzumab

Other:

• Phase I patients (closed to accrual as of 01/2004):

  • No prior serious hypersensitivity reactions after treatment with trastuzumab

• Phase I (closed to accrual as of 01/2004) and II patients:

  • No clinically significant active infection
  • No other unstable systemic disease
  • No other prior or concurrent malignancy except curatively treated carcinoma in situ of the cervix or basal cell skin cancer
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Phase I patients (closed to accrual as of 01/2004):

  • Prior trastuzumab (Herceptin) for metastatic disease allowed

• Phase II patients:

  • No prior trastuzumab for metastatic breast cancer

• Phase I (closed to accrual as of 01/2004) and II patients:

  • At least 4 weeks since prior immunotherapy
  • No other concurrent immunotherapy

Chemotherapy:

• Phase I patients (closed to accrual as of 01/2004):

  • Prior cytotoxic chemotherapy for metastatic disease allowed

• Phase II patients:

  • No prior cytotoxic chemotherapy for metastatic breast cancer

• Phase I (closed to accrual as of 01/2004) and II patients:

  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin; 12 weeks for anthracyclines or anthracenediones)
  • Prior adjuvant chemotherapy allowed
  • No prior cumulative dose of doxorubicin of more than 450 mg/m^2*
  • No prior cumulative dose of doxorubicin HCl liposome of more than 550 mg/m^2*
  • No prior cumulative dose of epirubicin of more than 700 mg/m^2*
  • No prior cumulative dose of mitoxantrone of more than 140 mg/m^2*
  • No concurrent chemotherapy NOTE: * Prior treatment with more than 1 of these drugs at dose levels below the limits listed above requires approval by the principal investigator

Endocrine therapy:

• See Disease Characteristics
• At least 4 weeks since prior hormonal therapy
• Prior hormonal therapy allowed in the adjuvant or metastatic setting
• No concurrent anticancer hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• Concurrent prophylactic doses of warfarin are allowed for maintaining patency of central line
• No other concurrent experimental anticancer medications
• No other specific antitumor therapy
• No concurrent CYP3A4 inhibitors