• Event-free survival as measured by clinical evaluation, CT scan, and bone scan imaging annually [ Designated as safety issue: No ]
  

• Overall survival [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the clinical efficacy of paclitaxel and cyclophosphamide followed by high-dose melphalan and high-dose etoposide with autologous peripheral blood stem cell rescue in patients with stage IIIB inflammatory breast cancer.
• Determine the effect of this regimen on T cells, in terms of number, phenotype, and cytokine profiles, in these patients.
• Determine the process of postchemotherapy T-cell regeneration in patients treated with this regimen.
• Determine the status of a number of key signal transduction pathways that may contribute to the inflammatory breast cancer phenotype.

OUTLINE:

• Induction chemotherapy: Patients receive induction chemotherapy comprising paclitaxel IV over 24 hours and cyclophosphamide IV over 1 hour on days 1-3. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once or twice daily beginning on day 5 and continuing until apheresis is completed. Treatment repeats every 29 days for up to 3-9 courses. Patients may receive up to 2 additional courses after their best response.

At the discretion of the investigator, patients may also receive up to 4 additional courses of doxorubicin IV and cyclophosphamide IV over 1 hour on day 1 every 21 days to complete induction therapy.

• Apheresis: Peripheral blood stem cells are harvested after the second course (and third course if necessary) of induction chemotherapy to collect adequate CD34+ numbers.
• Transplantation: Beginning at least 21 days after completion of induction chemotherapy, patients receive high-dose melphalan IV over 30 minutes and high-dose etoposide IV over 8 hours on days 1-3. Autologous peripheral blood stem cells are reinfused on day 7. Patients receive G-CSF SC once daily beginning on day 7.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for 2 years.

PROJECTED ACCRUAL: A maximum of 120 patients will be accrued for this study within 3.5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IIIB inflammatory breast carcinoma

  • Patients with no clinical inflammatory signs but with histologically confirmed tumor invasion of dermal lymphatics are eligible
  • No metastatic disease
• Previously untreated disease OR may have received prior induction chemotherapy outside the NCI provided patient did not fail initial chemotherapy regimen

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex

• Male or female

Menopausal status:

• Any status

Performance status:

• Karnofsky 70-100% OR
• ECOG 0-1

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 90,000/mm^3
• No history of abnormal bleeding tendency

Hepatic:

• Bilirubin less than 1.5 mg/dL (except in cases of Gilbert's disease)
• AST and ALT less than 3 times upper limit of normal
• Hepatitis B and C negative

Renal:

• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• Ejection fraction greater than 45% by MUGA or 2-D echocardiogram

Pulmonary:

• DLCO greater than 50%

Other:

• HIV negative
• No medical or psychiatric condition that would preclude study treatment
• No predisposition to repeated infections
• No active second malignancy except previously treated skin cancer or carcinoma in situ
• No history of diabetes mellitus
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• Prior neoadjuvant or adjuvant chemotherapy allowed
• Prior paclitaxel allowed

Endocrine therapy:

• No concurrent chronic steroids

Radiotherapy:

• No concurrent adjuvant radiotherapy

Surgery:

• Not specified

Other:

• No concurrent chronic anticoagulant therapy