Optimal management of brain metastases from breast cancer. Issues and considerations.

The incidence of brain metastases (BM) in breast cancer patients has increased over the last decade, presumably due to advances in systemic treatment. Today, breast cancer is the second most common cause of BM among all solid malignancies, second only to lung cancer; furthermore, it is the most common cause of leptomeningeal carcinomatosis. The HER2-positive subtype was consistently shown to have a higher risk for BM as compared with HER2-negative disease. More recently, however, it was shown that a similar incidence exists in triple-negative tumours. Local treatment options, radiotherapy and neurosurgical resection, remain the mainstay of therapy for BM. While some studies have suggested a direct effect of conventional chemotherapy on BM, the main beneficial aspect of systemic treatment is rather due to control of non-CNS systemic disease. Importantly, in patients with HER2-positive breast cancer receiving HER2-targeted therapy after local treatment for BM, superior survival outcomes were reported. Leptomeningeal carcinomatosis has a dismal prognosis. Survival with whole brain radiotherapy alone remains short and the potential additional benefit of intrathecal chemotherapy is still disputed. According to case reports, intrathecal administration of trastuzumab appears to be a promising strategy in patients with HER2-positive leptomeningeal carcinomatosis. In conclusion, while the outcome of breast cancer patients with BM has improved especially in the HER2-positive subtype, the prognosis for the majority of patients remains poor. Therefore, development of novel systemic treatment options offering activity within the brain is urgently warranted. Novel insights into the pathobiology of BM formation may offer the possibility for targeted drug prophylaxis of CNS involvement in high-risk patients.