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213,214 Specifically, disturbances in the circadian rhythm not only enhance the malignant potential of breast cancer cells (including their ability for self-renewal, replication, metastasis, and invasion) but also impact chemokine/chemokine receptor signaling (the CXCL12-CXCR4 axis may be the primary signaling pathway) which contributes to the formation of an immunosuppressive microenvironment ultimately leading to tumor progression