PURPOSE: To evaluate the duration and dose intensity of epirubicin-based 
regimens in premenopausal patients with lymph node-positive breast cancer.
PATIENTS AND METHODS: Between 1986 and 1990, 621 patients with operable breast 
cancer were randomly assigned to receive fluorouracil (Roche SA, Basel, 
Switzerland) 500 mg/m2, epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m2, and 
cyclophosphamide (Asta Medica AG, Frankfurt, Germany) 500 mg/m2 every 21 days 
(FEC 50) for six cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the 
same regimen with epirubicin 75 mg/m2 (FEC 75) for three cycles (3 FEC 75). All 
patients in the three arms received chest wall irradiation at the end of the 
third cycle.
RESULTS: After a 131-month median follow-up, the 10-year disease-free survival 
(DFS) was 53.4%, 42.5%, and 43.6% (P =.05) in the three arms, respectively. 
Pairwise comparisons demonstrate that 6 FEC 50 was superior both to 3 FEC 50 (P 
=.02) and to 3 FEC 75 (P =.05). The 10-year overall survival (OS) for the 6 FEC 
50 arm was 64.3%, for the 3 FEC 50 arm it was 56.6%, and for the 3 FEC 75 arm, 
it was 59.7% (P =.25), respectively. Pairwise comparisons demonstrate that 6 FEC 
50 was more effective than 3 FEC 50 (P =.10). Cox regression analysis 
demonstrates that OS was significantly better in the 6 FEC 50 than in the 3 FEC 
50 arm (P =.046). No severe infections (grade 3 to 4), acute cardiac toxicity, 
or deaths from toxicity have been observed. Only five patients developed delayed 
cardiac dysfunctions, and three patients developed acute myeloblastic leukemia.
CONCLUSION: After a long-term follow-up in an adjuvant setting, the benefit of 
six cycles of FEC 50 compared with three cycles, whatever the dose, is highly 
significant in terms of DFS. As regards OS, the group receiving six cycles of 
FEC 50 has significantly better results than the group receiving three cycles of 
FEC 50.