Cr. Sharpe, A DEVELOPMENTAL HYPOTHESIS TO EXPLAIN THE MULTICENTRICITY OF BREAST-CANCER, CMAJ. Canadian Medical Association journal, 159(1), 1998, pp. 55-59
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.