BCL-2 BUT NOT P53 EXPRESSION IS ASSOCIATED WITH RESISTANCE TO CHEMOTHERAPY IN ADVANCED BREAST-CANCER

Programmed cell death is an important determinant of the response to c hemotherapy, Among the factors controlling this process, a significant role is played by bcl-2 and p53, the expression of which, together wi th estrogen receptor content and tumor proliferative activity, was inv estigated by means of immunohistochemistry in 55 advanced breast cance r patients (median age, 60 years; range, 25-71 years). Analysis of bcl -2 expression identified two groups of patients with a significant dif ference in response rate. A total of 17 patients (31%) responded to ch emotherapy (5 had a complete response and 12 had a partial response): 14 of 32 (44%) bcl-2-negative patients (<40% stained cells) and only 3 of 23 (13%) bcl-2-positive patients (greater than or equal to 40% of stained cells; P = 0.019 by Fisher's exact test). The two groups were well balanced in terms of age, performance status, disease-free surviv al, menopausal status, and type of chemotherapy, bcl-2-negative tumors showed a tendency toward a higher p53 expression and proliferation ra te, whereas an excess of bone as the dominant disease site was evident among the bcl-2-positive ones, However, the only variable to result s ignificantly different between the two groups was estrogen receptor ex pression (P = 0.004). A multivariate logistic regression model showed that bcl-2 maintained its power of discriminating two groups with a di fferent probability of responding to chemotherapy, although the greate st contribution was given by dominant disease site and type of chemoth erapy. In conclusion, the results of this study suggest a possible rol e for bcl-2 in predicting resistance to chemotherapy.