Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients. An Eastern Cooperative Oncology Group trial.

The current trial was designed to assess whether the addition of prednisone or prednisone + tamoxifen would enhance the therapeutic effectiveness of 1 year of adjuvant CMF therapy. Premenopausal women with ipsilateral axillary node-positive breast carcinoma and known estrogen receptor (ER) status were randomized to receive 1 year of postoperative treatment with 12 28-day cycles of cyclophosphamide, methotrexate, 5-fluorouracil (CMF), CMF plus prednisone (CMFP), or CMFP plus tamoxifen (CMFPT). There were 553 analyzed cases with 188 receiving CMF, 183 CMFP, and 182 CMFPT. The overall time to relapse (TTR) and survival comparisons between the regimens are not statistically different at a median follow-up time of 7.7 years. The major subgroups currently with a suggestive TTR difference are greater than 3N+ (CMFPT greater than CMF, P = 0.07) and estrogen receptor-negative (ER-) greater than 3N+ (CMFPT greater than CMF, P = 0.03). Patients receiving CMFPT appeared to have a superior survival to CMF in the ER- greater than 3N+ cohort (P = 0.02). The following patient characteristics were associated with a significantly longer TTR: decreasing nodal involvement or tumor size, positive ER status, age greater than or equal to 40 years, and decreasing obesity. The favorable effects of decreasing nodal involvement, positive ER status, age 40 years or greater, and decreasing obesity carried over to survival. Development of amenorrhea was also significantly associated with improved survival (P = 0.001). Toxicity was increased by the addition of prednisone to CMF and by the addition of tamoxifen to CMFP. Overall relapse patterns were similar among the three regimens. The results of the current trial do not currently suggest an overall therapeutic benefit for adding prednisone or only 1 year of tamoxifen to CMF adjuvant treatment.