Combination Chemotherapy With or Without Trastuzumab Followed By an Autologous Stem Cell Transplant and Radiation Therapy in Treating Patients With Stage III or Stage IV Breast Cancer

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. An autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy with or without trastuzumab followed by an autologous stem cell transplant and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy with or without trastuzumab followed by an autologous stem cell transplant and radiation therapy works in treating patients with stage III or stage IV breast cancer.

OBJECTIVES:

* Determine the feasibility of tandem high-dose chemotherapy comprising melphalan, carboplatin, thiotepa, and cyclophosphamide with or without trastuzumab (Herceptin®) followed by autologous peripheral blood stem cell transplantation and helical tomotherapy or loco-regional radiotherapy in patients with high-risk stage IIIB, IIIC, or IV breast cancer.
* Determine the toxic effects of this regimen in these patients.

OUTLINE: Patients undergo stem cell collection.

* Course 1: Patients receive high-dose melphalan IV with or without trastuzumab (Herceptin®). One day later, patients undergo autologous peripheral blood stem cell (PBSC) transplantation. No more than 7 weeks later, patients proceed to course 2.
* Course 2: Patients receive high-dose carboplatin, thiotepa, and cyclophosphamide IV continuously over 4 days followed by autologous PBSC transplantation.

After recover from high-dose chemotherapy and autologous PBSC transplantation, patients with stage IIIB or IIIC disease undergo radiotherapy to the chest wall and lymph nodes. Patients with stage IV disease undergo radiotherapy using helical tomotherapy or standard radiotherapy to oligometastatic sites.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed breast cancer, meeting 1 of the following stage criteria:

  * Stage IIIB or IIIC disease, meeting both of the following criteria:

    * Must have received prior neoadjuvant or adjuvant therapy
    * Must have undergone lumpectomy or mastectomy
  * Stage IV disease, meeting all of the following criteria:

    * Only 1-3 organ sites with disease involvement after induction chemotherapy
    * Achieved at least a partial response after induction chemotherapy
    * No more than 3 lesions in the organ sites combined
* Inflammatory breast cancer allowed
* Completed chemotherapy, surgery, or radiotherapy for breast cancer within the past 6 months
* Hormone receptor status:

  * Not specified

PATIENT CHARACTERISTICS:

Age

* 65 and under

Sex

* Male or female

Menopausal status

* Not specified

Performance status

* Karnofsky 80-100%

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count ≥ 1,000/mm\^3
* Platelet count ≥ 100,000/mm\^3

Hepatic

* SGOT or SGPT ≤ 2 times upper limit of normal
* Bilirubin ≤ 1.5 mg/dL

Renal

* Creatinine ≤ 1.2 mg/dL
* Creatinine clearance ≥ 70 mL/min

Cardiovascular

* LVEF ≥ 55% by MUGA or echocardiogram

Pulmonary

* FEV_1 ≥ 60% of predicted
* DLCO ≥ 60% of the lower limit of predicted value
* Oxygen saturation \> 92% on room air

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No autoimmune disorders
* No immunosuppressive condition
* No other malignancy within the past 5 years

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior biologic therapy except trastuzumab (Herceptin®)

Chemotherapy

* See Disease Characteristics

Endocrine therapy

* Not specified

Radiotherapy

* See Disease Characteristics
* No prior radiotherapy to adjacent or involved sites of disease that would preclude study radiotherapy

Surgery

* See Disease Characteristics

Other

* No other concurrent anticancer therapy