Brain metastases are diagnosed in 16 to 25 percent of all women with breast cancer, but the brain is seldom the first site of relapse.15 Thus, while brain imaging with gadolinium-enhanced MRI is not part of the routine initial workup for newly diagnosed metastatic breast cancer, any patient with new neurologic complaints should be promptly evaluated. Most commonly, a progressively worsening headache develops over days to weeks. Other common clinical features of brain metastases include behavioral or cognitive changes, focal weakness, ataxia, speech disorders, and seizures.16
Papilledema is present in only 15 percent of patients, and the screening neurologic exam may be negative. Any of the above symptoms are thus indications for scheduling a gadolinium-enhanced MRI. Computed tomography (CT) scan is less sensitive and more likely to result in equivocal or false-positive findings. These scans cannot detect meningeal involvement and should only be obtained where MRI is unavailable.17
Corticosteroids, usually dexamethasone at a dosage of 4 mg every 6 hours, can produce immediate but shortlived improvement in neurologic symptoms and are indicated as initial treatment in all patients with strongly suspected or newly diagnosed brain metastases.18 Anti-convulsants, however, should be reserved for the 20 to 30 percent of patients who suffer focal or generalized seizures.19
Treatment of brain metastases may consist of either surgical extirpation, whole brain radiotherapy, or stereotactic "gamma-knife" radiosurgery. As retrospective analyses and a single randomized trial have demonstrated improved neurologic control and survival for patients undergoing surgery for brain metastases, resection must be the first consideration for all appropriate patients.20 The most appropriate candidates for resection have single, accessible lesions, particularly those that are relatively bulky and thus unlikely to respond completely to radiotherapy. The surgical candi date should also be one whose other sites of metastatic disease are responding, or are likely to respond to systemic therapy; for those whose expected survival is limited, surgical intervention has little or no advantage over radiotherapy.
Radiation therapy is indicated as initial palliative treatment for all other patients, for example, those with multiple lesions or poorly controlled systemic disease. Median survival for patients treated in this fashion is 3 to 6 months but a majority receive symptomatic benefit.21 Those who survive for > 1 year or longer after whole brain radiotherapy are at risk for a variety of complications ranging from subtle cognitive deficits to leukoencephalopathy manifesting as progressive dementia with ataxia. This is primarily a concern in good-risk patients and has made the use of adjuvant whole brain radiotherapy following surgical removal of a solitary brain metastasis controversial.
Stereotactic radiosurgery is a new technique that delivers a single, large, tightly focused dose of radiation to a metastatic site, using multiple beams. This technique is highly effective for tumors < 3 cm, can be performed on an outpatient basis, and appears to result in far less risk of long-term damage to surrounding normal tissue.22 While the current treatment of choice for recurrent disease after whole brain radiotherapy, and for patients with surgically inaccessible lesions, this technique may in time replace primary surgery for some patients.
Perhaps surprisingly, brain metastases from breast cancer have been reported to respond favorably to systemically administered chemo-therapy23 or tamoxifen.24 While currently no trials have established this as frontline therapy for brain metastases, this approach can certainly be tried in patients who relapse following whole-brain radiotherapy, or those who decline to undergo it.
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