TUMOR PROLIFERATIVE ACTIVITY AND RESPONSE TO FIRST-LINE CHEMOTHERAPY IN ADVANCED BREAST-CARCINOMA

The relationship between tumor proliferative activity and response to first-line chemotherapy and survival was investigated in 76 advanced b reast cancer patients. Proliferative activity was determined by means of Ki-67 immunohistologic staining on primary tumors (55 patients) or at the relapse site (21 patients), and was classified as low (less tha n or equal to 25% of stained cells) or high (> 25% of stained cells). The usual WHO response criteria were used. The median duration of foll ow-up was 18 months (range 3-58). Forty-seven patients (62%) had tumor s with low, and 29 (38%) had tumors with a high rate of proliferative activity. The two groups were well balanced in terms of important vari ables such as disease-free survival, performance status, age, menopaus al status, and the type of first-line chemotherapy (anthracycline-base d regimens versus cyclophosphamide-methotrexate-5-fluorouracil). The e strogen receptor (ER) content, measured by means of immunohistochemica l assay, was markedly different in the two groups, with 27/47 tumors w ith low proliferative activity (57%) and 6/29 with high-proliferative activity (21%) being ER positive (greater than or equal to 45% of stai ned cells) (p = 0.003). Moreover, a significant difference in the meta static pattern was also evident. with a higher incidence of bone and a lower incidence of soft tissue metastases in the group of patients wi th tumors with low proliferative activity (p = 0.004). Overall, 10/47 responses (21%: PR = 7, and CR = 3) were observed in the group with a low rate of proliferative activity, versus 14/29 (48%: PR = 9, and CR = 5) in the group with highly proliferative tumors, the difference bei ng statistically significant (p = 0.03). When a multivariate analysis was performed, the only factor that retained independent prognostic si gnificance was the predominant site of disease, particularly soft tiss ues (p = 0.003). Despite the difference in response rate, when surviva l analysis was performed according to the Kaplan-Meier method, no sign ificant difference was observed in the two groups, but when the analys is was limited to responsive patients, the median survival observed in those with a low and those with a high rate of proliferation was 35 a nd 19 months respectively (p = 0.02). The same results were obtained w hen multivariate survival analysis was carried out using Cox's regress ion model. These data suggest that there is a link between tumor proli ferative activity and response to chemotherapy in advanced breast canc er, and may indicate the need to use more intensive treatments in sele cted patients with highly proliferative tumors.