Pathology of breast cancer metastasis and a view of metastasis to the brain

Despite the advances in diagnosis and management of breast cancer, metastasis has been responsible for the staggering percentage of breast cancer-related death. Mortality threat can be explained mostly by the lack of proper understanding of the diversity of pathological features and underlying mechanism of breast cancer metastasis and effective targeted therapy. Breast cancer stem cells (BCSCs) are the potential source of tumor cells spread to distant organs. BCSCs targeted therapy can suppress the breast cancer progression to metastasis. Spreading of tumor cells to the bone, lung, liver, and brain occurs through a distinct non-random process; called metastasis organotropism. Recently, brain metastasis in breast cancer patients has been detected more frequently, causing a significant clinical burden. BRCA1 and BRCA2 associated breast cancers carry a remarkably higher propensity of CNS metastasis. BRCA1 and BRCA2 associated breast cancers commonly have the propensity to be the triple-negative (TN) and hormone receptors (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative molecular subtypes, respectively. Regardless of molecular subtypes, metastasis is most commonly evident at the bone. Heterogeneity is a critical pathological feature, leads to therapeutic resistance. BCSCs, biomarkers expression patterns, and mutations contribute to heterogeneity. In this paper, we discuss crucial pathological features of breast cancer metastasis, emphasizing metastasis organotropism and heterogeneity; and mechanisms of breast cancer metastasis, highlighting the pathways of metastasis to the brain. We consider that this paper reinforces future research areas and benefits the general readers, physicians, and researchers to identify potential areas to develop targeted therapies.