miRNAs as biomarkers for brain metastasis of breast cancer

Due to the rapid development of high-resolution imaging that allows clinicians to detect a primary tumor at an early stage, the survival of breast cancer patients has been significantly prolonged in the past decades. However, more than 90% of cancer deaths are still attributed to metastatic disease, and around 30% of patients with advanced stages of breast cancer develop brain metastasis [1,2]. Despite this clinical importance, the exact molecular mechanism of brain metastasis is as yet poorly understood, and we still lack a biomarker that helps in diagnosis and prognosis of this dreadful disease. Two subtypes of breast cancers have been shown to demonstrate a strong brain metastatic phenotype, HER2-positive and triple-negative (ER - PR - HER2 - ) tumors, and the median survival of these two subtypes are 3.7 and 9 months, respectively, compared with 15 months in the luminal subtype [3]. The consequences of brain metastasis are devastating, and the most common symptoms are constant headache, sensory disorder and seizures, which drastically impair the quality of life of both patients and their families. The primary approaches to treat patients with brain metastases include radiation therapy and surgery. However, due to the potentially serious side effects, technique feasibility needs to be taken into consideration before successful treatment. In the case of radiation therapy, stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are the most commonly used clinically, and in which high energy rays suppress tumor cell growth; however, these treatments may generate severe damage to the brain, such as physical trauma and cognitive malfunctions. Surgery is another option that only applies to patients with one or a few small lesions located in accessible regions. Chemotherapies have been widely used in treating both primary and metastatic tumors, and their effectiveness greatly depends on the stages