MULTISTEP PROGRESSION FROM AN ESTROGEN-DEPENDENT GROWTH TOWARDS AN AUTONOMOUS GROWTH IN BREAST CARCINOGENESIS

We investigated the relationship between hormone receptor status and c ellular proliferation in a series of proliferative epithelial breast l esions in an attempt to clarify the putative role of this interaction in the process of breast carcinogenesis. The separation of oestrogen r eceptor (ER) positive and ER negative cases revealed that in hyperplas tic breast epithelium (with and without atypia) the ER positive cases had a higher proliferation rate than that of ER negative cases. Conver sely, in ductal carcinomas (both in situ and invasive), ER negative ca ses had rates of proliferation higher than those observed among the ER positive cases. The observation of higher proliferation in ER positiv e benign proliferative breast lesions fits with the concept of an init ial hormone-dependent status in breast carcinogenesis. According to th is assumption, activation of ER by hormone increases the possibility t hat cells may undergo malignant transformation. Although we are limite d by our static view of the process, our results point to the existenc e of successive steps of progression from a hormone-dependent towards an autonomous growth. The demonstration of higher proliferation in ER- negative carcinomas, from the in situ phase onwards, reinforces the hy pothesis that breast cancer progression is paralleled by a progressive hormone independence.