• Phase I: To evaluate the safety, tolerability and and MTD of several dose levels of CPG 7909 of CPG 7909 in combination with the standard Herceptin® treatment in patients with metastatic breast cancer [ Designated as safety issue: Yes ]
• Phase II: Evaluate tumor response and safety of CPG 7909 in combination with Herceptin® in patients with metastatic breast cancer [ Designated as safety issue: No ]

• Safety will be assessed using dose-limiting toxicity guidelines, collection of adverse event information, evaluation of laboratory parameters, vital signs, physical examinations, ECOG performance status, and MUGA scan or echocardiogram.
• Efficacy endpoint will be overall tumor response rate. Tumor will be assessed by physical examination, CT, MRI, PET or bone scan and response will be determined using RECIST.

• Phase I: To evaluate tumor response, duration of response, time to disease progression, and survival time [ Designated as safety issue: No ]
• Phase II: To evaluate duration of response, time to disease progression, and survival time [ Designated as safety issue: No ]

The purpose of this study is to determine if the combination of CPG 7909 and Herceptin is safe and effective in the treatment of metastatic breast cancer.

RATIONALE: There is preclinical data that supports the hypothesis that CPG 7909 may potentiate the action of Herceptin. This Phase I/II study is designed to evaluate the safety and efficacy of the combination treatment of CPG 7909 and Herceptin in patients with metastatic breast cancer who have previously been treated with Herceptin and chemotherapy.

SCHEDULE: Patients will receive CPG 7909 weekly for up to six months.

Phase II part of study not initiated because the development plan modified the route of administration to subcutaneous injection.

• Drug: CPG 7909
• Drug: Herceptin®

• Experimental: 0.01 mg/kg CPG 7909 plus Herceptin®
• Experimental: 0.04 mg/kg CPG 7909 plus Herceptin®
• Experimental: 0.16 mg/kg CPG 7909 plus Herceptin®
• Experimental: 0.32 mg/kg CPG 7909 plus Herceptin®

INCLUSION CRITERIA Inclusion Criteria

• 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.
• Patients must be candidates for single agent Herceptin treatment according to the Herceptin® label.

Exclusion Criteria

• Any prior therapy with anthracycline + Herceptin®.
• 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%.