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Radiotherapy of CNS metastases in HER2 positive and triple negative disease

Brain metastases occur in about 30- 50% of patients with HER2 positive and 40% of patients with triple negative breast cancer. Occurrence of CNS metastases is a marker of aggressive disease. Median overall survival of patients with brain metastases is 13 – 19 months in patients with HER2 positive disease and 4.4 months in patients with triple negative disease. Regarding radiotherapy, breast cancer brain metastases are treated the same as metastases from all other tumor sites. When setting up an indication for local treatment, crucial is to have information about the control of extracranial disease, possibility of fur- ther systemic therapy lines and patient’s performance status. Local therapy consists of surgical treatment, with or without consolidation stereotactic radiotherapy and radiotherapy as a sole modality. Preferred method of radiotherapy would be stereotactic radiotherapy (SRT), in patients with up to 10-15 metastases, limiting factor being the volume of the disease (up to 15 mL). With STR local control can be achieved in up to 60% of patients. Fractionated stereotactic radiotherapy (FSRT), delivered in 3 to 12 fractions provides 1- year local control rate in up to 80% of patients. In case stereotactic radiotherapy is not available or pos- sible, patients with good performance status and extracranial disease control could be referred to whole brain radiotherapy (WBRT), which palliates symptoms in about 60% of patients. Both stereotactic and whole brain radiotherapy are connected with cognitive impairment, which is more often after WBRT. WBRT induced cognitive toxicity can be lowered by using hippocampal sparing radiation techniques. WBRT after SRT or neurosurgical procedure improves local control but has no effect on overall survival and can also lead to cognitive impairment. Therefore, WBRT is not indicated after these procedures. Upon neurosurgical operation, SRT of resection cavity should be performed, as it lowers the risk if intracranial relapse of the disease. There are several ongoing trials exploring different radiotherapy techniques (SRT or WBRT), and their timing and combination with various systemic agents in breast cancer patients with brain metastases, such as lapatinib, trastuzumab emtansine, pembrolizumab. In patients with low perfor- mance status, loss of extracranial disease control and short life expectancy, it would be reasonable to omit whole brain radiotherapy since it has no effect on survival or quality of life and the same palliative effect can be achieved with corticosteroids use only.

CNS metastases, HER2 positive breast cancer, triple negative breast cancer, radiotherapy, SRT, WBRT, FSRT

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