Local feedback mechanisms in human breast cancer

Breast function and development are controlled by a variety of both local a nd systemic signals. Many of these signals are exerted by hormones and cyto kines which are believed to be effectors in autoregulatory feedback loops. Recent studies have also suggested the involvement of such mechanisms in hu man breast cancer. For example, the disruption of a negative feedback syste m by malignant transformation can result in the loss of growth control or i n increased malignant behavior of tumor cells. Conversely, pathological pos itive feedback loops can develop that enhance tumor growth and invasion by excessive release of stimulatory factors. These loops are often located at the site of tumor invasion and involve stromal-epithelial interactions. The y can be composed of mutually stimulating or inhibiting cytokines and may i nclude locally expressed sex steroids. Although most studies have concentrated on cell-cell interactions at the si te of the primary tumor, a number of observations indicate their importance in metastases as well. A thorough analysis of the regulatory mechansims wi thin a malignant tumor is essential for the understanding of its unique beh avior and for the investigation of more specific breast cancer therapies.