Various factors contributing to tumor dormancy: Therapeutic implications in breast cancer

Cancer dormancy describes a stage in tumor progression where tumor cells survive in a quiescent state. Breast cancer is especially known for prolonged asymptomatic periods (up to 15-20 years) followed by a recurrence. Two main mechanisms of tumor cell dormancy are under discussion: Tumor cells cease dividing completely or persist proliferating at a slow rate counterbalanced by apoptosis. In the last decades, major efforts have been made to understand the process of interaction between circulating tumor cells (CTCs) in the bloodstream and their extravasation into distant sites, where CTCs may survive in a dormant state or acquire the ability to build metastases. Despite remarkable progress in this field, factors that determinate the fate of a single tumor cell remain to be clarified. An important hypothesis explaining the phenomenon of tumor cell dormancy is the stem cell theory. This theory indicates stem cell-like characteristics of at least a fraction of dormant CTCs that allows them to persist in the secondary sites and resist standard chemotherapies. Since dormant tumor cells are considered to cause relapse and metastases after long asymptomatic period, an understanding of their biology may be crucial for development of new therapeutic strategies to eradicate this distinct cell population and prevent recurrence. In this chapter we discuss biological mechanisms and clinical implications of tumor cell dormancy in breast cancer patients.