Analysis of Brain Metastasis in Patients With Breast Cancer, With and Without Over-Expression of HER-2

This study will examine two subsets of patients with breast cancer metastasis, that is, spreading, to the brain. It will identify genes and proteins that promote metastasis, particularly in women who are found to over-express (have more than other people do) the human epidermal growth factor receptor, ErbB2, also known as HER-2. The molecular and genetic events that permit tumor metastasis are not well understood. There is intense investigation going on into the process in which tumor cells escape the primary local tumor, spread to distant places in the body, and find and create conditions that promote growth in those tissues. Metastasis of tumors such as breast cancer to the brain is a common problem. Tumor cells will be analyzed with the use of microarrays. A microarray is a tool for analyzing gene expression, consisting of a small membrane or glass slide containing samples of many genes arranged in a regular pattern. The goal is to identify a potential molecular signature. It is hoped that there will be discovery of why some patients are more likely than others to develop a brain metastasis, which can have a major negative effect on the quality of life and survival. Female patients 18 years of age with known or evidence by radiology of a breast tumor metastatic to the brain or those who have had a removal of a brain tumor for diagnosis or treatment may be eligible for this study. Participants will undergo the following procedures and tests: * Craniotomy, that is, surgical opening of the skull, and removal of the brain tumor. * Blood specimens taken from a central vein or artery before the operation, throughout as needed, and for several days afterward, to measure blood chemistries, blood count, and so forth. * Physical examination and imaging of the central nervous system before and after surgery. * Urine or serum, or both, pregnancy test of women of childbearing potential. Patients will also undergo blood tests at 3-month intervals after surgery for up to 5 years. The purpose is to determine if there are tumor cells in the blood, which may explain how they reached the brain.

Sex

Female

Inclusion Criteria:

1. A woman with a known or with radiographic evidence of a breast neoplasm metastatic to the brain.
2. Medically-indicated (diagnostic and/or therapeutic) brain tumor resection.
3. Informed consent from female patient, age 18 or older. In general, patients less than 18 years of age rarely have breast cancer metastatic to the brain.

Exclusion Criteria:

1. Inability to provide informed consent prior to surgery.
2. Medical conditions that cannot be corrected prior to surgery that would be standard contraindications for craniotomy (brain tumor patients).
3. Men.

• BACKGROUNDSorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, Demeter J, Perou CM, Lonning PE, Brown PO, Borresen-Dale AL, Botstein D. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8418-23. doi: 10.1073/pnas.0932692100. Epub 2003 Jun 26. PMID 12829800
• BACKGROUNDPollack JR, Sorlie T, Perou CM, Rees CA, Jeffrey SS, Lonning PE, Tibshirani R, Botstein D, Borresen-Dale AL, Brown PO. Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12963-8. doi: 10.1073/pnas.162471999. Epub 2002 Sep 24. PMID 12297621
• BACKGROUNDSorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lonning PE, Borresen-Dale AL. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10869-74. doi: 10.1073/pnas.191367098. PMID 11553815