Recapitulation of a normal cellular growth program in early invasive breast-cancer

With a view to identifying markers reflecting not the evidence of, but the potential for, neoplastic progression of the breast we have compared the normal invasive mammary epithelial cell growth seen at puberty with invasive and non-invasive carcinogenesis using the mouse as a model. We have analyzed cell proliferation, the expression of the metalloproteinase stromelysin-1 and of the extracellular matrix protein tenascin. Striking parallels were observed between pubertal growth and the development of invasive, metastasizing mouse mammary tumors. In particular, the myoepithelial to epithelial transition of proliferation and stromelysin-1 expression was a hallmark of both normal growth at puberty and the early development of aggressive tumors. Investigation of neoplastic lesions in the human breast indicated that the pubertal growth characteristics are recapitulated only in the development of ductal carcinomas and may define early stages of invasive and potentially malignant growth.