INCLUSION

• Women > 18 years of age
• Histologically confirmed breast cancer with metastases
• Tumor that has overexpression of HER2 as documented by being either FISH-positive or HER2/neu 3+ confirmed by immunohistochemistry
• Eligible for Herceptin® therapy as a single agent.
• Up to three prior chemotherapy regimens for metastatic disease

Phase II only:

• Must have measurable disease by RECIST criteria (defined in section 8) with at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques, or as > 10 mm with spiral CT scan
• ECOG performance status of 0, 1 or 2
• Life expectancy of greater than 3 months
• Neutrophils >= 1,500/uL
• Platelets >= 100,000/uL
• Creatinine < 2mg/dL
• Bilirubin < 2mg/dL
• Transaminase < 2 times ULN

EXCLUSION

A patient must not be enrolled in the study, if any of the following criteria are met:

• Acute infection or fever over 38.2o Celsius within 3 days prior to study entry
• Any prior therapy with anthracycline + Herceptin® concurrently
• Significant cardiovascular disease (e.g., NYHA class 3 congestive heart failure, myocardial infarction within the past 6 months, unstable angina; coronary angioplasty within the past 6 months, uncontrolled atrial or ventricular cardiac arrhythmias) or left ventricular ejection fraction < 50%
• Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia
• History of allergic reactions attributed to compounds of similar composition to CpG 7909 and/or Herceptin® other than a mild hypersensitivity reaction commonly associated with the first infusion of Herceptin®
• Present significant renal, hepatic or pulmonary disease
• Known CNS metastases treated within 2 months of Day 1 or any uncontrolled CNS metastases

• Treatment with the following medications:

  1. Treatment with systemic corticosteroids within 4 week prior to the first dose of CpG 7909
  2. Immunostimulatory or immunosuppressive medications
  3. Monoclonal Antibodies, except Herceptin®
  4. Chemotherapy within 4 weeks of Day 1
  5. Radiation therapy within 4 weeks of Day 1
  6. Ongoing hormonal therapy that was initiated within 8 weeks of Day 1
  7. Chloroquine within 12 weeks of Day 1
• Any other medical history, including laboratory results, deemed by the investigator to be likely to interfere with participation in the study, or to interfere with the interpretation of the results
• Suspected or confirmed poor compliance or mental instability that may affect the patient's ability to sign the informed consent and undergo study procedures
• Participation in an investigational drug trial within 30 days prior to screening
• Patients who have not recovered from adverse events due to agents administered more than 30 days prior to study entry
• Lactating at time of study entry
• History of allogeneic transplants
• Known history of Hepatitis B or C (active, prior treated, or both)
• Known History of HIV