Normal breast: myths, realities, and prospects.

Abstract

Modern concepts of the breast acknowledge the extent of physiologic changes and attempt to relate them to pathogenesis. The natural life cycle of the lobule is incompletely understood, but the influences of the menstrual cycles, pregnancy, and involution are more clearly defined from morphologic studies. The extensive variety of modulating influences is a confounding factor, but an important principle is acceptance that breast and uterus respond differently to the mitogenic stimuli of steroid hormones. This has implications for the use of oral contraceptives and hormone replacement therapy. Greater understanding of the cytokines and growth factors that regulate cell cycle activity has potential relevance to the field of breast cancer chemoprevention. These and other pathways are now being explored more intensively in connection with the breast cancer genes BRCA1 and BRCA2. As the awareness increases of the complexities involved in cell signal transduction and transcription, it is useful to reflect on what evolution might tell us. A theory is developed herein to link the erect posture of humans with greater local breast estrogen synthesis and an inevitable association with cancer risk. The complex and variable structure of the breast requires cautious interpretations of conclusions reached with limited numbers or undue simplifications.