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Brain metastases are the most common intracranial neoplasm in adults. It is estimated that approximately 10% to 16% of patients with metastatic breast cancer will develop clinically evident brain metastases,1 while up to 30% of patients will have brain metastases identified at autopsy.2 Intraparenchymal metastases occur via hematogenous spread to the watershed area of the brain at the junction of the gray and white matter.3 The presence of metastases in the supratentorial and infratentorial compartments is in proportion to the relative weight and blood supply of these areas, with 85% occurring in the cerebral hemispheres, 10% to 15% in the cerebellum, and 1% to 3% in the brainstem.4 Leptomeningeal metastases are less common than intraparenchymal metastases and are found in 5% to 16% of patients at autopsy.1,2

Young age,5 estrogen receptor (ER)–negative status,6-8 the presence of pulmonary metastases,7 and HER-2 overexpression6,9 have all been described as risk factors for the development of brain metastases in patients with metastatic breast cancer. With improvements in systemic therapies and overall survival of patients with metastatic disease, the incidence of brain metastases appears to have increased over the last several years.10 In particular, with the introduction of trastuzumab, a humanized monoclonal antibody that binds to the extracellular segment of the HER-2/neu (erbB2) receptor and does not penetrate the blood-brain barrier,11 a higher incidence of central nervous system (CNS) metastases has been observed in patients receiving trastuzumab for metastatic breast cancer, ranging from 28% to 43%.9 This observation suggests that the incidence of CNS metastases may be higher in patients with HER-2-positive metastatic breast cancer whose systemic disease is well controlled with this newer agent.

Clinical Presentation

While some patients may be asymptomatic, the most common presenting symptom is headache, which can occur in 24% to 48% of patients.12,13 Other presenting signs and symptoms include nausea/vomiting (4%), gait ataxia (7%), focal weakness (20%), seizures (12%), speech difficulty and/or visual changes (5%), or impaired cognitive function (14% to 34%).12,14,15 Symptoms can be a result of the metastatic tumor itself, depending on the location, or from surrounding vasogenic edema. Cranial neuropathies suggest leptomeningeal involvement or invasion into the cavernous sinus.

Although the clinical suspicion of new onset brain metastases is higher in patients with known metastatic breast cancer, any patient with a history of breast cancer who presents with such signs or symptoms should undergo additional evaluation with a thorough neurologic examination and diagnostic imaging.

Diagnostic Imaging

Gadolinium-enhanced brain magnetic resonance imaging (MRI) is the best diagnostic test for brain metastases as it has been shown to be more sensitive than contrast-enhanced computed tomography (CT), particularly with respect to identifying lesions less than 10 mm and lesions in the posterior fossa.16...

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