On the Origin and Progression of Ductal Carcinoma in the Human Breast2

When 60 whole human breasts with and without coincident infiltrating ductal carcinoma were analyzed by a quantitative, three-dimensional subgross method correlated with histopathology, the smallest solitary, independent foci of ductal carcinoma in situ were observed in the terminal ductal-lobular units. If these independent foci are early stages of primary carcinoma, then a reasonable hypothesis is that ductal carcinoma in situ usually arises in these units, rather than in larger ducts. This hypothesis suggests that terminal ducts and/or lobules with atypical populations of .epithelial cells may be precancerous to common ductal breast cancer. A process of progressive lobular and ductular distension and unfolding, with concomitant coalescence of ductular lumens, probably explains the conversion of lobular structure (i.e., ductules) into larger ovoid and circular profiles. These profiles are of such magnitude that they sometimes falsely appear to be ducts in conventional, two-dimensional histologic slides.