RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of sequential high-dose chemotherapy followed by peripheral stem cell transplantation in treating patients with metastatic breast cancer that is responding to chemotherapy.

OBJECTIVES: I. Evaluate the feasibility and efficacy of sequential high-dose cyclophosphamide, melphalan, and thiotepa followed by peripheral blood stem cell rescue in patients with metastatic breast cancer who show a continuing response to prior conventional-dose chemotherapy.

PROTOCOL OUTLINE: All patients undergo peripheral blood stem cell (PBSC) collection using cyclophosphamide and granulocyte colony-stimulating factor (G-CSF). They then receive melphalan and thiotepa, each followed by PBSC re-infusion and G-CSF. Upon recovery from chemotherapy, patients with hormone receptor-positive tumors that are not refractory to hormonal therapy are treated with oral tamoxifen or megestrol. Patients may receive radiotherapy to prior bulky disease sites and/or undergo resection of residual lesions. Patients are followed weekly for 4 weeks, biweekly for 4 weeks, monthly for 6 months, then bimonthly for 1 year.

PROJECTED ACCRUAL: A minimum of 30 patients will be entered.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically documented breast carcinoma that is stage IV and considered incurable by standard treatment; Pathology reviewed by Yale-New Haven Hospital Department of Pathology
• Ongoing objective response to prior induction chemotherapy required
• No brain metastasis
• Hormone receptor status: Estrogen and progesterone status known

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior mitomycin or nitrosourea; At least 4 weeks since chemotherapy at time of stem cell harvest
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy to pelvis or brain
• Surgery: At least 2 weeks since major surgery

--Patient Characteristics--

• Age: Over 18
• Sex: Women or men
• Menopausal status: Not specified
• Performance status: Karnofsky 80%-100%
• Life expectancy: Greater than 3 months
• Hematopoietic: ANC greater than 1,500; Platelets greater than 100,000; Hemoglobin greater than 9 g/dL
• Hepatic: Bilirubin less than 1.5 times normal (unless benign congenital hyperbilirubinemia); PT and PTT normal; Liver biopsy normal if serologic evidence of active hepatitis B or C
• Renal: Creatinine no greater than 1.2 mg/dL
• Cardiovascular: No abnormal wall motion; No active heart disease; Left ventricular ejection fraction at least 50%
• Pulmonary: DLCO normal
• Other: Nutritional status adequate (greater than 1,000 calories/day orally); No HIV infection No other active serious medical or psychiatric disease; No other malignancy except: Basal cell skin carcinoma; In situ cervical cancer; Negative pregnancy test required of fertile women; Barrier method birth control required of fertile women throughout study and for up to 2 years thereafter