CHANGES IN BIOLOGICAL MARKERS AFTER PRIMARY CHEMOTHERAPY FOR BREAST CANCERS

The profiles of functional (proliferative rate and cell distribution i n the cell cycle) and phenotypic (nuclear DNA content and hormone rece ptor status) biological markers and the expression of P53 and Bcl-2 pr oteins 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 chan ge for slowly proliferating tumours. However, when considered as a fun ction of treatment type, changes of H-3-dT LI and FCM-S were superimpo sable in rapidly proliferating tumours, regardless of the type of trea tment, and in slowly proliferating tumours only after anthracycline-in cluding 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 pr oliferation indices could reflect different phenomena: an actual varia tion of proliferative activity by H-3-dT LI and an accumulation of cel ls in the S-phase by FCM-S. In addition, a higher accumulation of cell s in G(2)-M phases could be detected by FCM after anthracycline-includ ing regimens than after CMF. The fraction of P53-positive cells was re duced by primary chemotherapy in about 50% of P53-positive tumours, wh ereas Bcl-2 expression was only marginally affected. DNA ploidy and ho rmone receptor status did not change in about 75% of cases, regardless of the chemotherapeutic regimen. (C) 1995 Wiley-Liss, Inc.