Balance of cell proliferation and apoptosis in breast carcinogenesis

We determined the mitotic and apoptotic index through the spectrum of pre-i nvasive ductal breast lesions to invasive carcinoma in search of disturbanc es in the proliferation/cell death balance in breast carcinogenesis. Sevent y-two pure pre-invasive ductal breast lesions (without invasive carcinoma) and 103 invasive breast carcinomas were used. The numbers of mitotic and ap optotic cells were microscopically counted in hematoxylin and eosin stained sections (MI and Al, respectively), and the ratio of the values of MI and AI was calculated for each individual case (M/A index). A distinction was made between well differentiated and poorly differentiate d breast lesions, based on histological type and nuclear grade, to arrive a t two plausible progression models for breast carcinogenesis. For the well differentiated breast lesions, the MI was rather equal for hyperplasias and well differentiated DCIS, but increased 6-fold from DCIS to well different iated invasive carcinoma. The AI remained in the same range, resulting in a 4-fold increase of the M/A index. For the poorly differentiated breast les ions, a significant increase in MI and AI was found from hyperplasia to poo rly differentiated DCIS. From DCIS to poorly differentiated invasive carcin oma, the MI increased significantly and the AI decreased 2-fold (n.s.), res ulting in a 2.5-fold significant increase of the M/A index. In conclusion, the net increase of the number of cells in the transition fr om well differentiated pre-invasive to well differentiated invasive carcino ma is accompanied by an increase of cell proliferation rather than decrease in apoptosis, suggesting that in these lesions, proliferation related mech anisms are most important in carcinogenesis and progression. In contrast, i n poorly differentiated breast lesions, decreased apoptosis seems to be als o important in carcinogenesis and progression. At present, we are gathering patients with invasive breast cancer who had a previous biopsy with a pre- invasive lesion to obtain further more direct evidence for this hypothesis.