Biological Therapy in Treating Women With Stage IV Breast Cancer

DISEASE CHARACTERISTICS:

Phase I:

• Histologically confirmed infiltrating ductal carcinoma of the breast

• Metastatic disease

  • Clinically asymptomatic with non-life-threatening metastases allowed

• Measurable or evaluable disease by radiograph, CT scan, MRI, nuclear medicine bone scan, or physical examination

  • No measurable disease allowed if tumor or metastasis has been removed or successfully treated prior to study
• No rapidly progressive symptomatic disease affecting major organ systems (e.g., lungs and liver)
• Stable or unstable disease for 3 months on hormonal therapy
• Stable or unstable disease for at least 1 month after chemotherapy

• No active brain metastases

  • Brain metastases previously treated with definitive radiotherapy and/or surgical resection allowed

• Hormone receptor status:

  • Estrogen and progesterone receptor status known

Phase II:

• All Phase I criteria

• HER2/neu overexpression (2+ or 3+) by immunohistochemistry

  • Prior trastuzumab (Herceptin) allowed if disease still overexpresses HER2/neu

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Karnofsky 70-100% OR
• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 50,000/mm^3
• Hemoglobin at least 8 g/dL

Hepatic:

• Bilirubin less than 1.5 times normal
• SGOT less than 1.5 times normal

Renal:

• Creatinine no greater than 1.8 mg/dL
• Creatinine clearance at least 60 mL/min
• BUN no greater than 1.5 times normal

Cardiovascular:

• No myocardial infarction within the past year
• No prior myocardial infarction with coronary symptoms requiring medication and/or depressed left ventricular function (LVEF less than 50% by MUGA)
• No angina or coronary symptoms requiring medication and/or with depressed left ventricular function (LVEF less than 50% by MUGA)
• No congestive heart failure requiring medical management
• LVEF at least 50% at rest by MUGA
• No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg)

Pulmonary:

• FEV1, DLCO, and FVC at least 50% predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No other serious medical or psychiatric illness that would preclude study participation
• No other prior or concurrent malignancy within the past 5 years except curatively treated squamous cell carcinoma in situ of the cervix, basal cell skin cancer, or any other curatively treated disease in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• Prior trastuzumab allowed for phase I

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• See Disease Characteristics
• Concurrent hormonal therapy for breast cancer must continue during study
• No other concurrent hormonal therapy except steroids for adrenal failure, septic shock, or pulmonary toxicity or hormonal therapy for non-disease-related conditions (e.g., insulin for diabetes)

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics