OBJECTIVES:

• Assess the safety, toxicity, and feasibility of doxorubicin HCl liposome and docetaxel with or without trastuzumab (Herceptin™) in patients with metastatic breast cancer, particularly with respect to cardiotoxicity.
• Assess the overall objective response rate, response duration, time to treatment failure, and median survival of these patients with these treatment regimens.
• Assess any association between trough plasma levels of cardiac troponin T and brain natriuretic peptide and any cardiac event (congestive heart failure or LVEF decrease).

OUTLINE: Patients are assigned to one of two treatment arms according to HER2 overexpression status.

• Arm I (HER2 nonoverexpressed): Patients receive doxorubicin HCl liposome IV over 30 minutes followed by docetaxel IV over 1 hour. Treatment is repeated every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.

Patients may receive maintenance therapy of docetaxel IV over 1 hour either weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.

• Arm II (HER2 overexpressed): Patients receive trastuzumab IV over 90 minutes on day 1, with subsequent doses over 30 minutes. Patients receive doxorubicin HCl liposome IV over 30 minutes followed by docetaxel IV over 1 hour on day 2 of course 1, followed by subsequent doses on day 1 of each course. Antibody therapy continues weekly and chemotherapy every 3 weeks for 8 courses.

Patients may receive maintenance therapy of trastuzumab IV over 30 minutes weekly followed by docetaxel IV over 1 hour weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 92 patients (46 per arm) will be accrued for this study within 13 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic adenocarcinoma of the breast
• HER2 nonoverexpressed (0-1+) OR overexpressed (2-3+)

• Measurable or evaluable disease

  • Pleural or peritoneal effusions allowed if local intracavitary treatment not started at onset of therapy
  • Blastic or mixed blastic/lytic osseous metastases allowed if accompanied by pain or decreased performance status, and do not require radiotherapy within two courses of study therapy
  • Osteolytic disease allowed if proven by x-ray
  • No abnormal bone scan without confirmatory x-rays as only evidence of metastatic disease
• Prior brain metastases responsive to treatment of radiotherapy and/or surgery allowed (cannot be only site of metastases)

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• SGOT no greater than 2.5 times upper limit of normal
• Bilirubin normal

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No prior deep venous thrombosis or thromboembolic condition
• LVEF at least lower limit of normal
• No prior myocardial infarction or congestive heart failure
• No arrhythmia requiring medication
• No hypertension or systolic or diastolic dysfunction
• No ventricular hypertrophy or conduction abnormality

Pulmonary:

• No prior pulmonary thromboembolism

Other:

• No other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin
• Not pregnant or nursing
• Fertile women must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior trastuzumab (Herceptin™)

Chemotherapy:

• No prior chemotherapy for advanced or local/regional recurrent disease
• Prior adjuvant chemotherapy allowed if completed 6 months before metastasis
• No prior anthracyclines or anthracenediones

Endocrine therapy:

• At least 2 weeks since prior hormonal therapy

Radiotherapy:

• Prior radiotherapy allowed only to conserved breast, postmastectomy chest wall with or without internal mammary lymph node chain (IMN), or field containing less than 25% bone marrow
• No prior photon IMN treatment
• At least 2 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• At least 2 weeks since surgery (including mastectomy) and recovered