• INCLUSION CRITERIA:

Inclusion Criteria - Recipient:

1. Patients with measurable stage IV breast cancer. Patients with central nervous system CNS metastases are eligible if the CNS metastases have been treated and remained stable a minimum of four weeks after the completion of therapy.

2. Patients must have received at least one prior chemotherapy regimen for treatment of distant metastases and achieved less than a complete response to this therapy.

   1. Patients must have received prior therapy with a taxane (e.g. paclitaxel) and an anthracycline (e.g. doxorubicin) as part of either adjuvant therapy or treatment of metastatic disease.
   2. Patients whose tumor expresses estrogen and/or progesterone receptors must have received at least one hormonal therapy (e.g. Tamoxifen) as part of either adjuvant therapy or treatment of metastatic disease.
   3. Patients whose tumor expresses Her2-neu must have received trastuzumab (Herceptin ) as part of either adjuvant therapy or treatment of metastatic disease.
   4. Patients who have undergone prior autologous stem cell transplantation are eligible for this protocol.
3. Patients 18 - 75 years of age. The upper age limit was chosen in order not to be discriminatory, provided that patients meet all other eligibility criteria.
4. ECOG performance status less than or equal to 2 (Karnofsky performance status greater than or equal to 60%).
5. Life expectancy greater than 6 months.
6. Left ventricular ejection fraction has to be greater than or equal to 45% by either MUGA or 2-D echo. This test will repeated immediately after induction and prior to transplantation. Patients who do not have the minimally required function will be removed from trial.
7. DLCO greater than or equal to 50% of the expected value when corrected for Hb. This test will repeated immediately after induction and prior to transplantation. Patients who do not have the minimally required function will be removed from trial.
8. Creatinine less than or equal to 1.5 mg/dl and a creatinine clearance greater than or equal to 50 ml/min/1.73 m(2). This test will repeated immediately after induction and prior to transplantation. Patients who do not have the minimally required function will be removed from trial.
9. Direct bilirubin less than or equal to 2.5 mg/dl, SGOT less than 4x high normal value. Values above these levels may be accepted, at the discretion of the PI or study chairperson, if such elevations are thought to be due to liver involvement by malignancy. This test will repeated immediately after induction and prior to transplantation. Patients who do not have the minimally required function will be removed from trial.
10. Patients must be HIV-, HbsAg-, and Hepatitis C antibody negative. The high degree of immune suppression that will be used in this study may lead to the activation or progression of these viral illnesses.
11. Not pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. The effects of the chemotherapy, the subsequent transplant and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are unknown and may be harmful to the infant.
12. Consenting sibling matched at 6/6 HLA antigens.
13. Provision for a Durable Power of Attorney.
14. Ability to give informed consent.

Inclusion Criteria - Donor:

1. Age 18 - 75 years. As the potential for cerebrovascular and cardiac complications may potentially increase with age, 75 years has been chosen arbitrarily as the upper age limit. However, if it is determined after initial accrual of patients in this upper age range that this procedure is relatively safe, the age range may be extended.
2. No physical contraindications to stem cell donation (i.e. severe atherosclerosis, auto-immune disease, cerebrovascular accident, prior malignancy. Patients with severe atherosclerosis by history will receive a cardiology consult and be judged eligible on a case by case basis. The exclusion of patients with a prior malignancy will be evaluated on a case by case basis. If it is felt by the investigators that the risk of potential transfer of malignant cells is far outweighed by the potential benefit of the procedure the patient may be eligible to serve as a donor. Persons with a history of non-hematologic malignancy must have undergone potentially curative therapy for that malignancy and 1) have had no evidence of that disease for 5 years, and/or 2) be deemed at low risk for recurrence (less than or equal to 20% at 5 years). Such persons will be considered eligible for stem cell donation at the discretion of the principal investigator, who will evaluate the possible benefit to the potential transplant recipient and the risk of disease transmission in consultation with Department of Transfusion Medicine staff. Prospective donors with a history of non-hematologic malignancy who have received potentially curative therapy and are in remission, but whose estimated risk of recurrence is greater than 20% at 5 years, will be considered on an individual basis in consultation with the NCI IRB. Any prospective transplant recipient whose donor has a history of malignancy will be counseled about the theoretical risk of transmission of cancer from the donor to the recipient.
3. Donors must be HIV-negative, HbsAg, and Hepatitis C antibody negative. As donors are providing an allogeneic blood product there is the potential risk of transmitting these viral illnesses to the recipient.
4. Donor must not be pregnant or breastfeeding an infant. A donor who is lactating must substitute formula feeding for her infant during the period of cytokine administration. Filgrastim may be secreted in human milk, although its bioavailability from this source is not known. Limited clinical data suggest that short-term administration of filgrastim or sargramostim to neonates is not associated with adverse outcomes. Donors of childbearing potential must use an effective method of contraception during the time they are receiving cytokines. The effects of cytokine administration on a fetus are unknown and may be potentially harmful. The effects upon breast milk are also unknown and may potentially be harmful to the infant.
5. Ability to give informed consent.

EXCLUSION CRITERIA:

Exclusion Criteria - Patient

1. Active infection that is not responding to antimicrobial therapy.
2. History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent (as determined by principal investigator).

Exclusion Criteria - Donor

1. History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent.
2. History of hypertension that is not controlled by medication, stroke, or severe heart disease. Individuals with symptomatic angina will be considered to have severe heart disease and will not be eligible to be a donor.
3. Anemia (Hb less than 11 gm/dl) or thrombocytopenia (platelets less than 100,000 per ml).