OBJECTIVES:

• Determine the event-free survival of patients treated with high-dose chemotherapy with busulfan, melphalan, and thiotepa plus peripheral blood stem cell (PBSC) support followed by low dose immunotherapy with interleukin-2 (IL-2) and sargramostim (GM-CSF) for inflammatory stage IIIB and responsive stage IV breast cancer.
• Determine the toxic effects of this therapy in these patients.

OUTLINE: Peripheral blood stem cells (PBSC) are collected from the patient following stimulation with cyclophosphamide/paclitaxel/filgrastim (G-CSF) according to FHCRC 506 protocol or an approved FHCRC cytokine mobilization study. Patients must receive 1 course of cyclophosphamide and paclitaxel if cytokines alone are used to mobilize cells (FHCRC-506.03 protocol). G-CSF alone will be used to collect syngeneic PBSC (FHCRC-753).

Patients receive oral busulfan every 6 hours on days -8, -7, and -6. Melphalan IV is given on days -5 and -4 beginning at least 12 hours after busulfan. Thiotepa IV is given on days -3 and -2 followed by PBSC infusion on day 0 beginning 36-48 hours after the last dose of thiotepa.

All patients receive oral tamoxifen daily after transplant for 5 years or until relapse. Eligible patients receive interleukin-2 (IL-2) subcutaneously (SQ) daily plus sargramostim (GM-CSF) SQ on Monday, Wednesday, and Friday for 12 weeks beginning 30-100 days after transplantation. Patients with negative estrogen and progesterone status may discontinue tamoxifen therapy following IL-2/GM-CSF treatment. Patients receive radiotherapy after IL-2/GM-CSF treatment if no prior radiotherapy was given before transplantation.

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

PROJECTED ACCRUAL: Approximately 70 patients will be accrued for this study over 2 years.

DISEASE CHARACTERISTICS:

• Stage IIIB inflammatory breast cancer

  • Received 4-7 courses of doxorubicin or taxane based regimen

• Responsive stage IV breast cancer metastatic to soft tissue and/or bone

  • Partial or complete response after initial chemotherapy for metastatic disease
  • Received 4-7 courses of doxorubicin or taxane based regimen OR
  • Locally recurrent disease rendered disease free after surgery or radiotherapy
  • Bone disease responsive if demonstrated sclerosis of prior lesions with no new lesions
• Received 1 course of cyclophosphamide 4 g/m^2 and paclitaxel 250 mg/m^2 on protocol FHCRC-506.03
• Stem cell collection after mobilization with cyclophosphamide/paclitaxel or after an FHCRC approved cytokine protocol
• Syngeneic stem cells collected by using filgrastim (G-CSF) according to protocol FHCRC-753
• Adequate number of peripheral blood stem cells stored (at least 2,500,000 CD34+ cells)
• No CNS lesion (brain or carcinoid meningitis)

• Hormone receptor status:

  • Any status

PATIENT CHARACTERISTICS:

Age:

• 18 to 65

Menopausal status:

• Not specified

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 2 mg/dL
• SGOT or SGPT no greater than 2.5 times normal

Renal:

• Creatinine no greater than 2 mg/dL OR
• Creatinine clearance at least 50 mg/min

Cardiovascular:

• LVEF greater than 50%
• LVEF must be performed for symptoms of congestive heart failure, abnormal cardiac exam, or history of doxorubicin total dose greater than 400 mg/m^2

Pulmonary:

• No clinically significant pulmonary disease (diffusion capacity corrected less than 60% of predicted)

Other:

• Not pregnant
• HIV negative
• No history of seizures
• No hypersensitivity to E. coli preparations
• No active autoimmune disease
• No significant active infection precluding transplantation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior transplantation

Chemotherapy:

• See Disease Characteristics
• No more than 1 prior chemotherapy regimen for stage IV disease

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified