The origins of early breast carcinoma

Assessing the distribution of the in situ and invasive components of breast carcinomas and the extent of the disease represent an integrated part of our diagnostic routine. In this article, we summarize findings from 792 consecutive breast carcinoma cases, each documented in large-format histology slides. Selected cases were also analyzed in thick, large sections. Of these, 35.0% (42/120) of the purely in situ carcinomas were diffuse and occupied mostly larger ducts, whereas 37.5% (45/120) were multifocal and involved several distant terminal ductal-lobular units (TDLUs). The proportion of unifocal in situ cases involving a single TDLU or several neighboring TDLUs was 27.5% (33/120). Forty-one percent (136/332) of early (< 15 mm) invasive carcinomas and 40.0% (136/340) of larger invasive tumors contained only a single invasive focus, with or without an in situ component within it. The remaining tumors were nonunifocal because of multiple invasive or multiple in situ foci or both. The proportion of extensive nonunifocal cases within purely in situ, early invasive, and more advanced invasive cases were 45.0% (54/120), 42.5% (141/332), and 42.4% (144/340), respectively. The results are discussed in the context of recent molecular genetic findings and the sick lobe theory. Elements that are congruent with the classical views of Professor Azzopardi expressed over 3 decades ago will be pointed out. Breast carcinoma seems to develop within a field of genetic alterations, often at multiple sites, and a considerable proportion of the cases comprise extensive lesions occupying a tissue space > or = 40 mm in all tumor size categories.