The Immunoendocrine Network in Breast Cancer

Breast cancer is a disease in which abnormal cell proliferation leads to uncontrolled growth of breast tissue. Breast cancer can start in various areas of the breast, such as the ducts, lobes, and, in some cases, the intervening tissue. For many years, inflammatory infiltrates in tumors have been suggested to reflect the origin of cancer; however, little is known about the function of chronic inflammation in malignant transformation. Sex hormones are associated with many types of cancer, such as colon, cervical, and especially breast. Estrogen-dependent breast cancer (EDBC) constitutes approximately 50% to 80% of all cases of breast cancer. Furthermore, estrogen-dependency is linked to the initiation of malignancy by promoting the growth and proliferation of mammary cells and it is related to prognosis and treatment. The correlation between sex hormones and breast cancer has been recognized for decades, but the mechanisms of this association remain unknown. In recent years, a more enriched landscape of this relationship has emerged. Intervention by the immune system in cancer begins with the detection of transformed cells and their proliferation—not with the defense and effort to restrain an established tumoral mass. In the late 1950s, Burnet introduced the immunosurveillance theory, which proposes that immune system cells detect and attack transformed cells, eliciting an adaptive response that succeeds and eliminates them or fails, leading to the formation of a tumoral mass and cancer onset. Conversely, sex hormones are important modulators of the immune system. Growing evidence demonstrates a reciprocal relationship between sex steroids and the immune system. Because the innate immune response determines the type of adaptive immunity that develops, hormonal effects on the former can affect adaptive responses. The sex steroids estrogens, progesterone, and testosterone regulate the growth, differentiation, survival, and function of many cell types that mediate homeostasis, immunity, and breast cancer. The presence of sex steroid receptors on immune cells indicates that sex steroids exert their effects by binding to them. Sex steroids and immunity are inextricably linked, and their mutual regulation influences the maintenance of the immune balance. Understanding the mechanisms of action of sex steroids on immune cells is paramount to developing novel therapies for chronic diseases that are associated to immune dysregulation, such as breast cancer. This chapter describes the risk factors in breast cancer, the hormonal factors that are involved, the immunological response toward cancer, and the effects of sex steroids on immune system cells and their implications for the incidence of breast cancer.