The tumor microenvironment plays a pivotal role in the tumorigenesis, progression, and metastatic spread of many cancers including breast. There is now increasing evidence to support the observations that a bidirectional interplay between breast cancer cells and stromal cells exists within the tumor and the tumor microenvironment both at the primary tumor site and at the metastatic site. This interaction occurs through direct cell to cell contact, or by the release of autocrine or paracrine factors which can activate pro-tumor signaling pathways and modulate tumor behavior. In this review, we will highlight recent advances in our current knowledge about the multiple interactions between breast cancer cells and neighboring cells (fibroblasts, endothelial cells, adipocytes, innate and adaptive immune cells) in the tumor microenvironment that coordinate to regulate metastasis. We also highlight the role of exosomes and circulating tumor cells in facilitating breast cancer metastasis. We discuss some key markers associated with stromal cells in the breast tumor environment and their potential to predict patient survival and guide treatment. Finally, we will provide some brief perspectives on how current technologies may lead to the development of more effective therapies for the clinical management of breast cancer patients.

Claudins are the major component of the tight junctions in epithelial cells and as such play a key role in the polarized location of ion channels, receptors, and enzymes to the different membrane domains. In that regard, claudins are necessary for the harmonious development of a functional epithelium. Moreover, defective tight junctions have been associated with the development of neoplastic phenotype in epithelial cells. Breakdown of cell-cell interactions and deregulation of the expression of junctional proteins are therefore believed to be key steps in invasion and metastasis. Several studies suggest that the claudins are major participants in breast tumorigenesis. In this paper, we discuss recent advances in our understanding of the potential role of claudin 1 in breast cancer. We also discuss the significance of a subset of estrogen receptor negative breast cancers which express “high” levels of the claudin 1 protein. We propose that claudin 1 functions both as a tumor suppressor as well as a tumor enhancer/facilitator in breast cancer.

Breast cancer affects millions of women worldwide, leading to many deaths and significant economic burden. Although there are numerous treatment options available, the huge potentials of immunotherapy in the management of localized and metastatic breast cancer is currently being explored. However, there are significant gaps in understanding the complex interactions between the immune system and breast cancer. The immune system can be pro-tumorigenic and anti-tumorigenic depending on the cells involved and the conditions of the tumor microenvironment. In this review, we discuss current knowledge of breast cancer, including treatment options. We also give a brief overview of the immune system and comprehensively highlight the roles of different cells of the immune system in breast tumorigenesis, including recent research discoveries. Lastly, we discuss some immunotherapeutic strategies for the management of breast cancer.

Claudin 1 is a small transmembrane protein responsible for maintaining the barrier function that exists between epithelial cells. A tight junction protein that regulates the paracellular transport of small ions across adjacent cells, claudin 1 maintains cellular polarity and plays a major role in cell-cell communication and epithelial cell homeostasis. Long considered to be a putative tumor suppressor in human breast cancer, new studies suggest a role much more complex. While most invasive breast cancers exhibit a down regulation or absence of claudin 1, some aggressive subtypes that exhibit high claudin 1 levels have now been described. Furthermore, a causal role for claudin 1 in breast cancer progression has recently been demonstrated in some breast cancer cell lines. In this review we highlight new insights into the role of claudin 1 in breast cancer, including its involvement in collective migration and epithelial mesenchymal transition (EMT).