RATIONALE: Drugs used in chemotherapy, such as paclitaxel, cyclophosphamide, melphalan, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell transplant may allow more chemotherapy to be given so that more cells are killed.

PURPOSE: This phase I/II trial is studying the side effects of giving paclitaxel, cyclophosphamide, melphalan, and etoposide together with peripheral stem cell transplant and to see how well it works in treating patients with stage IIIB inflammatory breast cancer.

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.

• Biological: filgrastim
• Drug: cyclophosphamide
• Drug: doxorubicin hydrochloride
• Drug: etoposide
• Drug: melphalan
• Drug: paclitaxel
• Procedure: bone marrow ablation with stem cell support
• Procedure: peripheral blood stem cell transplantation

• Hakim FT, Memon SA, Cepeda R, Jones EC, Chow CK, Kasten-Sportes C, Odom J, Vance BA, Christensen BL, Mackall CL, Gress RE. Age-dependent incidence, time course, and consequences of thymic renewal in adults. J Clin Invest. 2005 Apr;115(4):930-9. Epub 2005 Mar 17.
• Sportes C, McCarthy NJ, Hakim F, Steinberg SM, Liewehr DJ, Weng D, Kummar S, Gea-Banacloche J, Chow CK, Dean RM, Castro KM, Marchigiani D, Bishop MR, Fowler DH, Gress RE. Establishing a platform for immunotherapy: clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients. Biol Blood Marrow Transplant. 2005 Jun;11(6):472-83.

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