CHANGES IN BIOLOGICAL MARKERS AFTER PRIMARY CHEMOTHERAPY FOR BREAST CANCERS

The profiles of functional (proliferative rate and cell distribution in the cell cycle) and phenotypic (nuclear DNA content and hormone receptor status) biological markers and the expression of P53 and Bcl-2 proteins were prospectively evaluated in breast cancers before and after different regimens of primary chemotherapy. Overall, changes induced on the 2 proliferation indices (H-3-thymidine labelling index, H-3-dT LI, and flow-cytometric S-phase fraction, FCM-S) mainly consisted of a decrease for rapidly proliferating tumours and an increase or no change for slowly proliferating tumours. However, when considered as a function of treatment type, changes of H-3-dT LI and FCM-S were superimposable in rapidly proliferating tumours, regardless of the type of treatment, and in slowly proliferating tumours only after anthracycline-including regimens. Conversely, following CMF, FCM-S was increased in 90% of the cases and H-3-dT LI in only 50%. Our data imply that the 2 proliferation indices could reflect different phenomena: an actual variation of proliferative activity by H-3-dT LI and an accumulation of cells in the S-phase by FCM-S. In addition, a higher accumulation of cells in G(2)-M phases could be detected by FCM after anthracycline-including regimens than after CMF. The fraction of P53-positive cells was reduced by primary chemotherapy in about 50% of P53-positive tumours, whereas Bcl-2 expression was only marginally affected. DNA ploidy and hormone receptor status did not change in about 75% of cases, regardless of the chemotherapeutic regimen. (C) 1995 Wiley-Liss, Inc.