Cyclophosphamide and Vaccine Therapy with or without Trastuzumab in Treating Patients with Stage IV Breast Cancer

Inclusion Criteria

• Patients with histologically confirmed adenocarcinoma of the breast that does not over-express HER-2/neu; this is defined as fluorescent in situ hybridization (FISH) negative, or 0, 1+ or 2+ by immunohistochemistry (IHC); IHC 2+ tumors must be FISH negative with an amplification ratio of less than 2.0; patients must not be eligible for therapy of known curative potential for metastatic breast cancer if it is identified during the course of the study
• Patients must have measurable or evaluable Stage IV breast cancer
• Stable central nervous system (CNS) disease that has been adequately treated and is not under active treatment allowed
• Able to give informed consent
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
• No systemic oral steroids administered within 28 days prior to initiating treatment on protocol; topical, ocular, and nasal steroids are allowed, as are those applied to mucus membranes
• No prior or currently active autoimmune disease requiring management with systemic immunosuppression; this includes inflammatory bowel disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia or immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, sarcoidosis, or other rheumatologic disease; asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids is acceptable
• Not pregnant, and on appropriate birth control if of child-bearing potential
• No history of other malignancies within the prior five years (excluding a history of carcinoma in situ of the cervix, superficial non-melanoma skin cancer, superficial bladder cancer, or Tamoxifen-related endometrial cancer that has been adequately treated)
• Absolute neutrophil count (ANC) > 1000
• Platelets > 100,000
• Serum creatinine < 2.0
• Serum bilirubin =< 2.0; serum bilirubin > 2.0 is acceptable in the setting of known Gilbert’s syndrome
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2 x the upper limit of normal
• Alkaline phosphatase =< 5 x the upper limit of normal
• Adequate cardiac reserve with a cardiac ejection fraction within the lower limit of facility normal by multi-gated acquisition (MUGA), or 50% by echocardiogram
• No active major medical or psychosocial problems that could be complicated by study participation
• Human immunodeficiency virus (HIV) negative

Exclusion Criteria

• No histologic documentation of breast adenocarcinoma
• Breast adenocarcinoma that is amplified for HER-2/neu gene expression by 2-fold or more by FISH analysis, or that is IHC 3+
• Cardiac dysfunction documented by an ejection fraction less than the lower limit of the facility normal by MUGA scan, or less than 50% by echocardiogram
• Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest
• History of autoimmune disease as detailed above
• Systemic oral corticosteroid treatment within 28 days prior to initiating treatment on study
• Uncontrolled medical problems
• Evidence of active acute or chronic infection
• Previous vaccination with the allogeneic GM-CSF-secreting breast tumor vaccine
• Chemotherapy, radiation therapy, or biologic therapy (except trastuzumab) within 28 days prior to initiating treatment on study; endocrine therapy and supportive therapy with bisphosphonates will be allowed
• Participation in an investigational new drug trial within 28 days prior to initiating treatment on study
• Pregnant or breast feeding
• Hepatic, renal, or bone marrow dysfunction as detailed above
• Concurrent malignancy or history of other malignancy within the last five years except as noted above
• Corn allergy
• Known severe hypersensitivity to trastuzumab (excluding mild to moderate infusion reactions that are easily managed and do not recur)