REDUCED APOPTOSIS AND PROLIFERATION AND INCREASED BCL-2 IN RESIDUAL BREAST-CANCER FOLLOWING PREOPERATIVE CHEMOTHERAPY

Experimental laboratory data suggest that tumour growth is a balance b etween apoptosis and proliferation and that suppression of drug-induce d apoptosis by oncogenes such as bcl-2 may be an important cause of in trinsic chemoresistance. The aims of this study were to assess the in vivo relationship of apoptosis to proliferation and Bcl-2 protein in h uman breast tumours both prior to chemotherapy and in the residual res istant cell population at the completion of treatment. We examined apo ptotic index (AI), Ki67 and Bcl-2 protein expression in the tissue of 40 patients with operable breast cancer immediately before ECF preoper ative chemotherapy, and in 20 of these patients with residual tumour, at the completion of treatment. There was a significant positive assoc iation between AI and Ki67 both before and after chemotherapy, and in their percentage change with treatment, In the residual specimens AI a nd Ki67 were significantly reduced compared with pre-treatment biopsie s, while Bcl-2 expression showed a significant increase, No difference s were seen in the pre-treatment levels of any of the variables measur ed between patients obtaining pathological complete response and those who did not, although numbers were small. These data suggest that apo ptosis and proliferation are closely related in vivo. It is possible t hat the phenotype of reduced apoptosis and proliferation, and increase d Bcl-2 may be associated with breast cancer cells resistant to cytoto xic chemotherapy, although this can only be proven by assessing larger numbers of patients in relation to pathological response.