The Eastern Cooperative Oncology Group (ECOG) trial of adjuvant
cyclophosphamide,
methotrexate,
fluorouracil, and
prednisone (CMFP) or CMFP plus
tamoxifen (
CMFPT) for 1 year compared with observation alone in 265 postmenopausal patients with node-positive
breast cancer is reported with 74 months median follow-up. Overall relapse-free survival tended to favor
CMFPT (P = .08), but no survival differences existed between any treatment group. The addition of
tamoxifen to CMFP led to slightly (but not significantly) better relapse-free status in all subgroups analyzed. Subgroup analysis based on stratification variables showed significant benefit from CMFP (+/- T) only in
estrogen receptor (ER)-negative patients with respect to disease-free status (P = .0003), but not survival (P = .54). Relapse-free status was actually worse for CMFP-treated patients with ER-positive
tumors, but not significantly so (P = .15). By multivariate analysis other significant risk factors for relapse-free status were primary
tumor size, number of nodes pathologically involved, and the number of nodes examined. ER status was prognostic only for the observation group with the benefit from
chemotherapy on ER-negative patients obliterating this difference in treated patients. Survival was affected by the number of involved nodes,
tumor size, presence of
tumor necrosis, and patient
obesity. Analysis of toxicity showed elevation of liver
enzymes during the first year to be more common in the observation group compared with those patients receiving adjuvant treatment and to be associated with early recurrence. Toxicity from adjuvant treatment persisted beyond termination of
therapy in 53% of patients, but was usually mild and self-limited. We conclude
CMFPT offers relapse-free survival benefit in ER-negative patients, but the value of
chemotherapy in ER-positive postmenopausal, node-positive patients must be questioned.