BIOLOGICAL HETEROGENEITY OF ER-POSITIVE BREAST CANCERS IN THE POSTMENOPAUSAL POPULATION

In the natural history of post-menopausal patients with primary breast cancer, high estrogen receptor levels (ER) have been associated with a poor recurrence-free survival. The purpose of this study was to inve stigate whether there are any biological intratumoral characteristics to support this puzzling clinical observation. In a population of 542 post-menopausal, primary-breast-cancer patients, 3 normal distribution s fitted into the frequency distribution curve of the logarithmically transformed ER-EIA values. The biological profiles of the low ER group , and of the intermediate and high ER groups identified in the ER-posi tive population were compared. Parameters correlated with ER functiona l aspect (progesterone receptors adn PS2), receptors of epidermal grow th factor (EGFR), protease cathepsin D and tumor proliferation (deduce d from thymidine kinase activity) were analyzed. As previously reporte d, the levels of progesterone receptors and PS2 increased significantl y from the low to the high ER groups. The highest levels of cathepsin D and thymidine kinase which have been previously related to a poor pr ognosis in breast cancer were found in the low ER group, but high leve ls were, surprisingly, also found in the high ER group. This study ind icates that the ER-positive post-menopausal population is biologically heterogeneous. The high levels of thymidine kinase found in the high ER group suggest that overexpression of ER may be associated with prol iferation enhancement, partly explaining the poor spontaneous prognosi s related to this subset. (C) 1994 Wiley-Liss, Inc.