Despite diagnostic advances, breast cancer remains the most prevalent cancer among women in the United States. The armamentarium of treatment options for metastatic disease is limited and mostly ineffective with regards to eradicating cancer. However, there have been novel findings in the recent literature that substantiate the function of the microenvironment in breast cancer progression and the support of metastasis to tertiary sites such as bone marrow. The uncovered significance of the microenvironment in the pathophysiology of breast cancer metastasis has served to challenge previously widespread theories and introduce new perspectives for the future research to eradicate breast cancer. This paper delineates the current understanding of the molecular mechanisms involved in the interactions between breast cancer cells and the microenvironment in progression, metastasis, and dormancy. The information, in addition to other mechanisms described in bone marrow, is discussed in the paper. 1. Introduction The ability to invade and metastasize allows cancer cells to leave sites of primary tumor formation and recolonize in new tissues. This offers immediate metastasis to distant sites as well as the establishment of dormancy. Metastases are responsible for approximately 90% of human cancer deaths [1]. The previously established theory on metastasis described the phenomenon as a process alike to the Darwinian evolution [2]. In that perspective, cancer cells undergo a process of natural selection which favors rare cells within a tumor capable of invading and growing at sites of metastasis. The natural selection was believed to involve the development of stable genetic alterations which proffer the potential for successful metastasis. However, advances in technology, especially the development of high-throughput microarray expression profiling and in vivo imaging, have served to challenge this perspective of cancer metastasis [2]. Research suggests that metastatic ability is gained at earlier stages of tumor expansion than predicted by the previous model, and that this ability is acquired through transient changes in gene expression. A new tumor microenvironment invasion model reconciles the Darwinian perspective with recent discoveries. The tumor microenvironment consists of surrounding stroma, which is composed of extracellular matrix and various cell types including endothelial cells, fibroblasts, and infiltrative leukocytes. The microenvironment, in addition to providing a scaffold for the organ, has been found to play a significant role in breast cell
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