The theory of the sick breast lobe and the possible consequences.

We hypothesize that carcinoma in situ, and consequently breast carcinoma in general, is a lobar disease because the simultaneously or asynchronously appearing, often multiple tumor foci develop within a single lobe. The sick lobe carries some kind of genetic instability already from its initialization during the early embryonic life and is more sensitive to noxious influences than the other lobes within the same breast. Decades of postnatal life with accumulation of additional genetic alterations are needed for malignant transformation of the cells within the sick lobe. The transformation is often multifocal (involving separate distant lobules of this lobe) or diffuse (involving the larger ducts). This hypothesis offers new perspectives in cancer prevention, because selective visualization, excision, or destruction of the sick lobe before development of malignant lesions would substantially reduce the incidence of breast carcinoma.