The predictive value of estrogen receptor (ER) level for response to chemotherapy was studied in 182 patients with metastatic breast cancer in a prospective study. Patients were stratified according to ER status and dominant site of disease and randomized to one of three regimens: cyclophosphamide, 5-Fluorouracil, and prednisone (CFP) versus CFP, methotrexate, and vincristine (CFPMV) versus doxorubicin and cyclophosphamide (AC). There was no significant differences in all response categories (P = 0.21), duration of remission (P = 0.07), and survival (P = 0.17) among the three regimens. When ER status was taken as a predictor for response to chemotherapy, there was no significant difference in overall response (P = 0.61) between ER+ (62/108, 57%) and ER-patients (31/49,63%). However, there was a significant trend toward a higher degree of response in ER-patients (more complete response [CR] nine of 49, 18%, and fewer failures six of 49, 12%) than in ER+ (less CR seven of 108, 7%, and more failures 37/108, 34%) (P = 0.006). Patients with higher measured levels of ER showed worse response (Kendall's tau C, P = 0.026). This trend for ER-patients to have better response than ER+ patients was generally consistent, regardless of the predominant site of metastases or chemotherapy regimen (P = 0.04 for CFP; P = 0.08 for CFPMV; and P = 0.20 for AC). The advantage of a better response for ER-patients was nullified by an earlier relapse which was reflected in longer duration of remission, time to treatment failure, and survival in favor of ER+ patients (12.3 months versus 7.3 months remission duration, 18.7 months versus 13.6 months survival in partial responders). These data suggest that ERpatients respond to a higher extent to chemotherapy but relapse sooner than ER+ patients, suggesting a more rapid growth for ER-tumors. In patients with ER-tumors and poorer prognosis on conventional chemotherapy, new trials of intensive consolidation after response should be considered.
Cancer 64:6-15, 1989.
HE ROLE of estrogen receptor (ER) status in predict-T ing the response to hormonal manipulations in metastatic breast cancer has been well documented in the last decade.'-3 Its role in responses to chemotherapy, however, has not been clearly defined and has become a controversial issue. There is still today no consensus regarding its significance. Some investigators have found that ER-negative patients had a significantly increased response to cytotoxic chemotherapy,'-6 whereas others have indicated the