Breast Cancer Brain Metastases: Genetic Profiling and Neurosurgical Therapy

Abstract

Brain metastases occur in 10–15% of patients with metastastic breast cancer. The annual incidence in the USA and Europe is in the range of 5–10 per 100,000 per year. The mean latency period between diagnosis of the primary tumor and the detection of brain metastases is 2–3 years. Most often, brain metastases arise at the white/grey matter border in the supratentorial space. The standard imaging is contrast-enhanced magnetic resonance imaging (MRI). Treatment consists in open surgical resection and/or stereotactic radiosurgery. It is appropriate to resect 1–3 accessible lesions within 1–2 operations. Adjuvant radiotherapy is applied on a routine basis. Chemotherapy might be applied according to the primary tumor. Overall median survival is in the range of 5.5–14.5 months. Research activities in this field include molecular profiling of breast cancer brain metastases. We have attempted genetic cDNA array profiling using a 15 K microarray of brain-selective MDA-MB-231 cells. These have been acquired from multiple passages of MDA-MB-231 invasive and metastastic breast cancer cells in mice. Profiling of selective metastatic cells showed accumulation of gene expression characteristic for brain metastasis. Several factors were identified which are potentially important for this process: Metastasis-Suppressor Gene KiSS-1, Matrix-Metallo-Proteinase-(MMP)-1 and vascular factor endoglin. Further structural and functional studies in selective metastastic cells and human specimens were undertaken. These results underline the importance of these factors for the molecular process of breast cancer brain metastasis.