• The goal of this clinical research study is to see if Herceptin (trastuzumab) and GM-CSF can help to shrink or slow the growth of breast cancer that has spread outside the breast, which did not respond to earlier treatment with Herceptin. [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
  

• The safety of this treatment will also be studied. [ Time Frame: 6 Years ] [ Designated as safety issue: Yes ]
  

GM-CSF stimulates the immune system and may increase the effectiveness of Herceptin.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have a complete medical history and physical exam. This includes blood tests (about 2 tea spoons), and x-rays. Women who are able to have children must have a negative blood or urine pregnancy test.

If you are found to be eligible to take part in this study, you will receive trastuzumab through a vein every week until the disease gets worse. GM-CSF will be injected under the skin at least once a day until the white blood cell count is stable. GM-CSF will also continue during the course of study until the disease progresses.

You will have further evaluation of your disease by CT scan, bone scan, chest X-ray, etc. at 2, 4, 6, 9, 12, 18, and 24 months after the start of treatment. You will have blood tests (about 2 tea spoons) at least twice a week until the appropriate dose of GM-CSF is found. The dose may increase or decrease depending on the blood test.

You will have blood (about 2 tablespoons) drawn before treatment at the 2nd and 4th month, and if the disease gets worse.

You will be removed from the study if the disease is progressing or severe side effects occur.

This is an investigational study. The FDA has approved trastuzumab and GM-CSF, but their use in this study is experimental. GM-CSF will be provided by Berlex free of charge during this study. A total of 36 patients will take part in this study. All will be enrolled at UTMDACC.

Inclusion Criteria:

1. Histological confirmation of invasive carcinoma of the breast.
2. HER-2/neu overexpression: 3+ by immunohistochemical staining or FISH (+).
3. Stage IV breast cancer with measurable disease.
4. Patient receiving progressive disease after Herceptin plus chemotherapy or Herceptin alone. No more than two Herceptin containing regimens.
5. Zubrod performance status 0 or 1.
6. Adequate hematological parameters (WBC > 3,000/mm3, platelet count > 100,000/mm3), adequate renal function (serum creatinine < 2.0 mg/dl), adequate liver function (total bilirubin, SGOT & SGPT < 3 x normal).

Exclusion Criteria:

1. Active Brain metastasis.
2. No measurable disease at the time of registration (e.g. bone only, leptomeningeal disease alone or pleural effusion alone).
3. More than 2 Herceptin containing regimens in metastatic breast cancer.
4. Known history of HIV positive.
5. Chronic active hepatitis or cirrhosis.
6. Symptomatic pulmonary disease.
7. Use of steroid of non-steroidal anti-inflammatory analgesic or Cox-2 inhibitor 1 week prior to registration.