A randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer

The sequential doxorubicin → CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF × 6 cycles (CMF); (b) doxorubicin × 4 cycles followed by CMF × 6 cycles (A → CMF); (c) CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years (CMF → GT); and (d) doxorubicin × 4 cycles followed by CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years (A → CMF → GT). The study used a 2 × 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A → CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A → CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556–0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489–1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555–0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54–1.32). A → CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients.