CXCR4 and neoplasm: Disruptions to the normal circadian rhythm can increase the risk of breast cancer.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.