A DEVELOPMENTAL HYPOTHESIS TO EXPLAIN THE MULTICENTRICITY OF BREAST-CANCER

IN THIS ARTICLE THE AUTHOR PROPOSES that the multicentricity of breast cancer might be explained by a developmental hypothesis. Genetic alte rations (''hits'') occurring in epithelial stem cells during the devel opment of the breast may be transmitted to populations of daughter cel ls during growth. As a result, areas of the breast may be predisposed to malignant transformation with the occurrence of further genetic hit s. Areas with the same predisposition should be anatomically connected , and earlier hits during breast development should result in larger a reas of predisposition. The multicentricity of breast cancer would be explained if multiple lesions - monoclonal for the predisposing geneti c hit and polyclonal for subsequent hits - developed within a predispo sed area. Multiple lesions arising from the spread of disease by exten sion would be expected to share many genetic hits. The author discusse s the implications that further evidence supporting the developmental hypothesis would have for the prevention and treatment of breast cance r.