Timing of Radiation Therapy and Chemotherapy After Breast-Conserving Surgery for Node-Positive Breast Cancer: Long-Term Results From International Breast Cancer Study Group Trials VI and VII

Abstract

To update the previous report from 2 randomized clinical trials, now with a median follow-up of 16years, to analyze the effect of radiation therapy timing on local failure and disease-free survival. From July 1986 to April 1993, International Breast Cancer Study Group trial VI randomly assigned 1475 pre-/perimenopausal women with node-positive breast cancer to receive 3 or 6 cycles of initial chemotherapy (CT). International Breast Cancer Study Group trial VII randomly assigned 1212 postmenopausal women with node-positive breast cancer to receive tamoxifen for 5years, or tamoxifen for 5years with 3 early cycles of initial CT. For patients who received breast-conserving surgery (BCS), radiation therapy (RT) was delayed until initial CT was completed; 4 or 7months after BCS for trial VI and 2 or 4months for trial VII. We compared RT timing groups among 433 patients on trial VI and 285 patients on trial VII who received BCS plus RT. Endpoints were local failure, regional/distant failure, and disease-free survival (DFS). Among pre-/perimenopausal patients there were no significant differences in disease-related outcomes. The 15-year DFS was 48.2% in the group allocated 3months initial CT and 44.9% in the group allocated 6months initial CT (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.87-1.45). Among postmenopausal patients, the 15-year DFS was 46.1% in the no-initial-CT group and 43.3% in the group allocated 3months initial CT (HR 1.11; 95% CI 0.82-1.51). Corresponding HRs for local failures were 0.94 (95% CI 0.61-1.46) in trial VI and 1.51 (95% CI 0.77-2.97) in trial VII. For regional/distant failures, the respective HRs were 1.15 (95% CI 0.80-1.63) and 1.08 (95% CI 0.69-1.68). This study confirms that, after more than 15years of follow-up, it isreasonable to delay radiation therapy until after the completion of standard CT.