RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with cyclosporine and paclitaxel may be an effective treatment for metastatic breast cancer.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy, cyclosporine, and paclitaxel in treating patients who have recurrent or refractory metastatic breast cancer.

OBJECTIVES:

• Determine the maximum tolerated dose of yttrium Y 90 monoclonal antibody m170 in combination with cyclosporine and paclitaxel in patients with recurrent or refractory metastatic breast cancer.
• Determine the preliminary efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study of yttrium Y 90 monoclonal antibody m170 (Y90 MOAB m170).

Patients receive filgrastim (G-CSF) subcutaneously (SC) daily for 4 days prior to apheresis which continues daily for a maximum of 5 days. A minimum of 6 million CD34+ cells/kg must be harvested.

Patients receive oral cyclosporine every 12 hours on days -3 to 25. Patients receive unlabeled monoclonal antibody (MOAB) m170 IV followed by a tracer dose of indium In 111 MOAB m170 IV on day 0. On day 7, patients receive unlabeled MOAB m170 IV followed by Y90 MOAB m170 IV. Patients in cohorts 2-4 also receive paclitaxel IV over 3 hours on day 9.

If needed, patients undergo autologous peripheral blood stem cell transplantation on day 21 and receive G-CSF SC daily until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of Y90 MOAB m170 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed monthly for 3 months, every 3 months for 1 year, and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 18-30 patients will be accrued for this study within 36 months.

• Biological: filgrastim
• Biological: monoclonal antibody m170
• Drug: cyclosporine
• Drug: paclitaxel
• Procedure: peripheral blood stem cell transplantation
• Radiation: yttrium Y 90 monoclonal antibody m170

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed metastatic breast adenocarcinoma

  • Residual or recurrent disease after first-line standard chemotherapy
  • Clinical evidence of metastatic disease
• Tumor cells positive for m170 immunoreactivity
• HAMA titer negative

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Not specified

Menopausal status:

• Not specified

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

Renal:

• Creatinine less than 1.5 mg/dL

Cardiovascular:

• LVEF at least 50% by MUGA

Pulmonary:

• FEV1 at least 65% of predicted
• FVC at least 65% of predicted
• DLCO at least 60%

Other:

• No other malignancy within the past 5 years except nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Chemotherapy

Chemotherapy:

• See Disease Characteristics
• At least 1 prior chemotherapy regimen for advanced disease
• Prior high-dose chemotherapy with autologous stem cell transplantation is allowed if given at least 12 months prior to study and carmustine was not used
• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior external beam radiotherapy
• No prior radiotherapy to more than 25% of the total skeleton

Surgery:

• Not specified

Other:

• No requirement for oral anticoagulants (low-dose warfarin for central line thrombosis prophylaxis allowed)