Phase II Study of Tetrathiomolybdate (TM) in Patients With Breast Cancer

Inclusion Criteria:

1. Patients must have histologically confirmed breast malignancy that is:

• High risk stage II breast cancer (≥4 positive lymph nodes),

• Stage III breast cancer, including inflammatory breast cancer

• Stage IV breast cancer in a complete remission (bone only not allowed unlessthe bone scan is normal).

2. The patient must have had what is considered standard adjuvant systemic therapy thatmay include chemotherapy, hormonal therapy and radiation therapy. They may haveundergone high dose chemotherapy with stem cell support as part of their therapy inthe adjuvant or metastatic setting. The patient is allowed to continue to takeadjuvant hormonal therapy (for high risk adjuvant patients) and may be allowed to beon hormonal consolidation post transplant if they are without evidence of diseaseafter a transplant for metastatic breast cancer. The patient cannot be activelyreceiving chemotherapy or any biologic agent to treat their breast cancer.

3. Six weeks must elapse from last chemotherapy or radiation therapy.

4. The patient must have had definitive surgical therapy for their breast cancer. Thisincludes lumpectomy and axillary dissection or mastectomy.

5. No clinical or radiologic evidence of disease after surgery and/or systemictreatment (by CT scan of chest, abdomen and pelvis and bone scan or PET scan priorto enrollment)

6. Because no dosing or adverse event data are currently available on the use of TM inpatients < 18 years of age, children are excluded from this study.

7. ECOG performance status < 1

8. Life expectancy of greater than 3 months.

9. Patients must have normal organ and marrow function as defined below:

• hemoglobin >10mg/dL

• absolute neutrophil count >1,500/mL

• platelets >100,000/mL

• total bilirubin < 1.5 x normal institutional limits

• AST(SGOT)/ALT(SGPT) <1.5 X institutional upper limit of normal

10. Erythropoietin alpha is allowed, as indicated.

11. Bisphosphonates may be administered if they were started prior to starting thistherapy.

12. Patients must be on stable medical therapy for at least 2 weeks if they are beingtreated medically for their peripheral neuropathy.

13. Concurrent herceptin is not allowed.

14. The effects of TM on the developing human fetus are unknown. For this reason, womenof child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry andfor the duration of study participation. Should a woman become pregnant or suspectshe is pregnant while participating in this study, she should inform her treatingphysician immediately.

15. Ability to understand and the willingness to sign a written informed consentdocument.

Exclusion Criteria:

1. Patients who have had chemotherapy or radiotherapy within 6 weeks prior to enteringthe study.

2. Objective evidence of breast cancer.

3. Carcinomatous meningitis or history of neoplastic parenchymal brain disease.

4. Serum creatinine >1.5 x normal.

5. History of allergic reactions attributed to compounds of similar chemical orbiologic composition to TM.

6. Pregnant women are excluded from this study because TM has the potential to haveteratogenic or abortifacient effects. Because there is an unknown but potential riskfor adverse events in nursing infants secondary to treatment of the mother with TM,breastfeeding should be discontinued if the mother is treated with TM.

7. Because patients with immune deficiency are at increased risk of lethal infectionswhen treated with marrow-suppressive therapy, HIV-positive patients receivingcombination anti-retroviral therapy are excluded from the study because of possiblepharmacokinetic interactions with TM.