In general, the development of CNS
metastases of
breast cancer depends on several prognostic factors, including younger age and a negative
hormone receptor status. Also, the presence of a
breast cancer 1, early onset (BRCA1) germline mutation and expression of the
human epidermal growth factor receptor 2 (Her2/neu) proto-oncogene seem to contribute to an increased rate of development of CNS
metastases. The choice of appropriate
therapy for
brain metastases also depends on prognostic factors, including the age of the patient, the Karnofsky performance score, the number of
brain metastases and the presence of systemic disease. Surgery followed by whole brain
radiation therapy (WBRT) is generally restricted to ambulant patients with a single brain
metastasis without active extracranial disease. In patients who have two to four
metastases, stereotactic focal
radiotherapy (i.e. radiosurgery) with or without WBRT is usually indicated. In the remainder of patients, WBRT alone provides adequate palliation. Although
breast carcinoma is sensitive to
chemotherapy, the role of
chemotherapy in the treatment of
brain metastases is still unclear. Objective responses after
cyclophosphamide-based
therapies were reported in studies performed in the 1980s. Subgroup analysis of data from a randomised study indicates that survival may improve if WBRT is combined with the radiosensitiser
efaproxiral. Interestingly, the Her2/neu antibody
trastuzumab, which does not cross the blood-brain barrier, produces systemic responses and enhanced survival, without a clear effect on
brain metastases.
Breast cancer constitutes the most common solid primary tumour leading to leptomeningeal disease. Clinical symptoms such as cranial nerve dysfunction or a
cauda equina syndrome can be treated with local
radiotherapy. A randomised study in patients with leptomeningeal disease secondary to
breast cancer has revealed that intrathecal
chemotherapy is associated with substantially more adverse effects than non-intrathecal treatment, without a clear benefit in terms of response or survival. Intramedullary
metastasis is rare but often presents with a rapidly progressive
myelopathy. Local
radiotherapy may preserve neurological function. Epidural spinal cord
metastasis occurs in approximately 4% of patients and can lead to
paraplegia. A randomised study has shown that surgical intervention together with local
radiotherapy is superior to local
radiotherapy alone.