Breast cancer metastasis to the central nervous system

Abstract

Clinically symptomatic metastases to the central nervous system (CNS) occur in approximately 10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding.

Figure 1

Representative manifestations of breast cancer metastasis to the brain. A: Solitary metastasis (∼1 cm in size) to the brain demonstrated by MRI (T1-weighted, axial, postgadolinium image). The tumor is in the posterior right frontal lobe. B: The tumor (arrow) is surrounded by a significant amount of peritumoral edema (T2-weighted axial MR image). C and D: Multiple metastasis to the brain before (C) [demonstrated by MRI (T1-weighted images with the administration of gadolinium for contrast)] and after (D) surgical resection (axial computed-tomography scan with contrast; arrows in D indicate the location of the resection). The tumor in the left frontal region was intraparenchymal and the tumor in the left parieto-occipital region was dural-based. E: Miliary metastases demonstrate multiple, contrast-enhancing lesions on a single T1-weighted, gadolinium-enhanced MRI slice, ranging in size from 2 to 3 mm to 1 cm. F: Carcinomatous meningitis. Multiple linear enhancing tongues of tumor can be seen outlining the cerebellar folia on theT1-weighted gadolinium-enhanced MRI.

Figure 2

Representative mechanistic image of the BBB. The BBB is created by the snug apposition of endothelial cells that line the brain. This creates the barrier between the vascular system and the brain parenchyma. This is reinforced by numerous pericytes. A thin basement membrane surrounds the endothelial cells and provides both structural support and a dense physical barrier between the circulation and the microenvironment of the brain. Commonly, astrocytes extend cellular processes that cover the basement membrane, further limiting the ability of macromolecules or circulating cells to gain access to the CNS. Reprinted with the permission of The Cleveland Clinic Foundation.