The MIG-1 trial, an Italian multicentre Phase 3 randomised study, investigated the long-term efficacy and safety of dose-dense (DD) versus standard-interval FEC chemotherapy in high-risk early breast cancer patients. From 1992 to 1997, 1214 patients were randomised to receive six cycles of FEC chemotherapy every 2 (FEC14) or 3 (FEC21) weeks. The primary endpoint was overall survival (OS), with secondary endpoints including event-free survival (EFS) and distant disease-free survival (DDFS).
At a median follow-up of 15.8 years, the study found that 15-year OS was 71% in the FEC14 group and 68% in the FEC21 group (HR = 0.89; p = 0.25). The 15-year EFS was 47% in the FEC14 group and 43% in the FEC21 group (HR = 0.87; p = 0.18). Notably, among patients with hormone receptor-negative tumors, the FEC14 group showed a 15-year OS of 70% compared to 65% in the FEC21 group (HR = 0.73; 95% CI: 0.51–1.06), and a 15-year EFS of 58% versus 43% (HR = 0.70; 95% CI: 0.51–0.96).
The study concluded that updated results from the MIG-1 trial are numerically in favor of DD chemotherapy, suggesting a long-term benefit of this approach in high-risk early breast cancer patients. The findings are particularly relevant for patients with hormone receptor-negative and HER2-positive tumors, indicating that DD chemotherapy may be more effective in these subgroups. However, the study also acknowledges limitations, including early closure and underpowered statistical analysis due to lower than expected mortality rates. Despite these limitations, the long-term results support the sustained benefit of DD chemotherapy over at least 15 years.
