Breast Cancer Dormancy – Lessons Learnt

Despite early diagnosis and improved treatments, breast cancer remains a challenging disease. A strategic advantage for breast cancer recurrence is the ability of breast cancer cells to become quiescent and survive for decades in a dormant state within the endosteal region of the bone marrow. Breast cancer dormancy is triggered by exosome vesicles secreted by mesenchymal stem cells residing in the bone marrow. By mechanisms yet to be determined, dormant breast cancer cells are awakened leading to resurgence and metastasis. Experimental evidence supports the notion that dormant breast cancer cells are cancer stem cells recognized as tumor initiating and propagating cells with chemoresistant and metastatic properties. These cells represent less than 2% of the total tumor mass, which impose a significant barrier for their therapeutic targeting. This review focuses on cellular and molecular properties of breast cancer dormancy including tumor microenvironment, epigenetic regulation, cell signaling and metabolic reprogramming.