In breast cancer, an uncontrolled cell proliferation leads to tumor formation and development of a multifactorial disease. Metastasis is a complex process that involves tumor spread to distant parts of the body from its original site. Metastatic dissemination represents the main physiopathology of cancer. Inter-and intracellular communication in all systems in vertebrates is mediated by cytokines, which are highly inducible, secretory proteins, produced not only by immune system cells, but also by endocrine and nervous system cells. It has become clear in recent years that cytokines, as well as their receptors are produced in the organisms under physiological and pathological conditions; recently, they have been closely related to breast cancer metastasis. The exact initiation process of breast cancer metastasis is unknown, although several hypotheses have emerged. In this study, we thoroughly reviewed the role of several cytokines in breast cancer metastasis. Data reviewed suggest that cytokines and growth factors are key players in the breast cancer metastasis induction. This knowledge must be considered with the aim to development of new therapeutic approaches to counter breast cancer metastasis.

Organism homeostasis is regulated through the tri-directional relationships between immune, endocrine, and nervous systems. These relationships are established by a complex network of chemokines, cytokines, hormones (peptide and non-peptide), neurotransmitters, and neurohormones that act onto its target cells, through common receptors. Despite initial attribution of the exclusive action of each molecule group (neurotransmitters, hormones, and cytokines), to the function of one specific system (nervous, endocrine, and immune, respectively), ligand and receptor pleiotropy and redundancy showed the multidirectional communication between systems. Cancer and metabolic and autoimmune diseases get established when homeostasis is disrupted. These interactions act in different disease levels, in cancer, since initial immunosurveillance phase, until immunosubversion and metastasis, in all cases is crucial for tumor development, cancer outcome, and patient prognosis.