Multistep progression from an oestrogen-dependent growth towards an autonomous growth in breast carcinogenesis

We investigated the relationship between hormone receptor status and cellular proliferation in a series of proliferative epithelial breast lesions in an attempt to clarify the putative role of this interaction in the process of breast carcinogenesis. The separation of oestrogen receptor (ER) positive and ER negative cases revealed that in hyperplastic breast epithelium (with and without atypia) the ER positive cases had a higher proliferation rate than that of ER negative cases. Conversely, in ductal carcinomas (both in situ and invasive), ER negative cases had rates of proliferation higher than those observed among the ER positive cases. The observation of higher proliferation in ER positive benign proliferative breast lesions fits with the concept of an initial hormone-dependent status in breast carcinogenesis. According to this assumption, activation of ER by hormone increases the possibility that cells may undergo malignant transformation. Although we are limited by our static view of the process, our results point to the existence 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 hypothesis that breast cancer progression is paralleled by a progressive hormone independence.