Exemestane With or Without ATN-224 in Treating Postmenopausal Women With Recurrent or Advanced Breast Cancer

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer
• Recurrent disease after 2-3 years of adjuvant treatment with an anti-estrogen (documented by imaging techniques)
• Advanced disease that has recurred during or after anti-estrogen therapy
• Measurable or evaluable disease by conventional techniques, with ≥ 1 lesion that can be followed for response
• Bone metastases only are eligible provided they have ≥ 1 lytic lesion (not previously irradiated or planned for irradiation) that can be followed by X-ray or CT scanning
• Cutaneous skin metastases only are eligible provided the skin lesions are > 10 mm and can be followed by good quality photography with a ruler included in the photograph
• No clinically apparent brain metastases
• Hormone receptor status must meet 1 of the following criteria:
• Estrogen receptor-positivity
• Score ≥ 3 on a scale (range of 0 to 8), or equivalent score from other grading methods, representing the intensity and percentage of positive-staining tumor cells by immunohistochemistry
• Greater than or equal to 5 fmol/mg protein by ligand binding assay or ELISA
• Progesterone receptor-positivity
• Score ≥ 3 on a scale (range of 0 to 8) or equivalent score from other grading methods, representing the intensity and percentage of positive-staining tumor cells by immunohistochemistry
• No HER-2 overexpression, defined as gene amplification by fluorescence in situ hybridization [FISH] OR 3+ overexpression by IHC)

PATIENT CHARACTERISTICS:

• Postmenopausal as defined by any of the following:
• Surgical or radiation-induced
• No menstrual periods for 12 consecutive months with no other biological or physiological cause in women with an intact uterus
• Age ≥ 55 years
• WHO performance status 0-2
• Life expectancy ≥ 6 months
• Hemoglobin ≥ 9.0 g/dL
• ANC ≥ 1.5 x 10^9/L
• Platelet count ≥100 x 10^9/L
• Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and/or AST ≤ 2.5 times ULN (5 times ULN if due to tumor)
• Creatinine clearance ≥ 50 mL/min
• No history of malabsorption syndromes or other gastrointestinal disorders that may affect SOD1 inhibitor ATN-224 absorption, including any of the following:
• Bowel obstruction
• Celiac disease
• Sprue
• Cystic fibrosis
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to SOD1 inhibitor ATN-224, omeprazole (or other proton pump inhibitor), or exemestane
• No non-malignant systemic disease including active uncontrolled infection
• No serologic positivity for hepatitis B, hepatitis C, or HIV
• No concurrent congestive heart failure
• No history of NYHA class III-IV cardiac disease
• No other concurrent malignancy, except adequately treated cone-biopsied carcinoma in situ of the uterine cervix, basal cell or squamous cell carcinoma of the skin
• Cancer survivors who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 5 years, and are deemed at low risk for recurrence are eligible
• No other condition which, in the investigator's opinion, would not make the patient a good candidate for this study

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from all prior therapy (alopecia allowed)
• At least 1 year since prior bilateral oophorectomy
• Prior adjuvant or neoadjuvant treatment with tamoxifen allowed
• Prior adjuvant therapy with a non-steroidal aromatase inhibitor allowed
• More than 4 weeks since prior immunotherapy or chemotherapy (6 weeks for nitrosoureas and mitomycin-C)
• More than 4 weeks since prior major thoracic and/or abdominal surgery
• More than 3 weeks since prior endocrine therapy
• More than 4 weeks since prior and no concurrent radiotherapy (except to control pain or prevent fracture)
• No prior exemestane
• Concurrent iron-containing vitamins or supplements are allowed
• No concurrent luteinizing hormone-releasing hormone analog
• No concurrent oral bisphosphonates (IV bisphosphonates allowed)
• No concurrent chronic steroid therapy for concurrent illness or cancer (short-term steroid use for concurrent illness allowed [e.g., for acute asthma])
• No concurrent copper- or zinc-containing vitamins or supplements
• No concurrent participation in another interventional clinical study (participation in an observational study allowed)
• No other concurrent copper-binding drug (e.g., penicillamine or trientine)
• No other concurrent anticancer therapy or investigational agent