Figure 1.

(A) Stages of breast development. The breast is unique in that full maturation of the breast does not occur until later in life, after puberty. During puberty, the female breast undergoes rapid changes: proliferating terminal end buds and elongation of the ducts promote the formation of primitive lobular structures and growth of the ductal tree. Breast development illustrations courtesy of the University of California Davis School of Medicine, Robert Cardiff MD, PhD, and Hannah Jensen MD (open source information) [15]. (B) The high-risk field hypothesis is that specific genetic or epigenetic alterations may occur in a breast progenitor cell prior to, or during puberty, and the clonal expansion of a damaged progenitor during puberty would result in a localized predisposed terminal ductal lobular unit (TDLU) or “high-risk” field, from which breast cancer subsequently would arise. A second genetic or epigenetic “hit” in a high-risk field is hypothesized to survive and propagate with a higher frequency than a similar “hit” in a normal breast lobule.