IntroductionBreast cancer is genetically and clinically a heterogeneous disease [1], [2], [3], and metastatic lesions are the leading cause of death in patients [4], [5], [6], [7]. Accumulating evidence suggests that the tumor bulk of breast cancer contains a heterogeneous tumor cell population that is derived from a subset of cells that show the characteristics of stem cells, termed as tumor-initiating cells or cancer stem cells (CSCs) [8], [9]. The whole course of tumor metastasis is a complex procedure requiring the most aggressive cancer cells rather than all tumor cells to be able to survive the long time circulation and to form new local lesions by extravasation and migration. Accumulating evidence indicates that CSCs play a key role in not only the original tumorigenicity but also in their ability for local invasion and migration [10], [11], [12]. Overlapping with some features of normal stem cells, CSCs are shown to be resistant to proapoptotic factors, rendering them a formidable adversary to current anti-cancer modalities [13], [14], [15]. Extensive studies have demonstrated that breast cancer stem cells (BCSCs) exhibit the ability to metastasize to specific parts of the body and are believed to be a cause for metastatic lesions. Although it is expected that the tumor heterogeneity and BCSCs may be the last obstacles for effective breast cancer treatment, the molecular insights and potential specific biomarkers for the therapy-resistant BCSCs need to be further elucidated before potential clinical benefits could be achievable.