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Purpose: To determine whether a boost to the tumor bed after breast-conserving surgery (BCS) and radiotherapy (RT) to the whole breast affects local control and disease-free survival. Methods and Materials: A total of 1,138 patients with pT1 to pT2 breast cancer underwent adjuvant RT at the University of Florence. We analyzed only patients with a minimum follow-up of 1 year (range, 1–20 years), with negative surgical margins. The median age of the patient population was 52.0 years (±7.9 years). The breast cancer relapse incidence probability was estimated by the Kaplan-Meier method, and differences between patient subgroups were compared by the log rank test. Cox regression models were used to evaluate the risk of breast cancer relapse. Results: On univariate survival analysis, boost to the tumor bed reduced breast cancer recurrence (p < 0.0001). Age and tamoxifen also significantly reduced breast cancer relapse (p = 0.01 and p = 0.014, respectively). On multivariate analysis, the boost and the medium age (45–60 years) were found to be inversely related to breast cancer relapse (hazard ratio [HR], 0.27; 95% confidence interval [95% CI], 0.14–0.52, and HR 0.61; 95% CI, 0.37–0.99, respectively). The effect of the boost was more evident in younger patients (HR, 0.15 and 95% CI, 0.03–0.66 for patients <45 years of age; and HR, 0.31 and 95% CI, 0.13–0.71 for patients 45–60 years) on multivariate analyses stratified by age, although it was not a significant predictor in women older than 60 years. Conclusion: Our results suggest that boost to the tumor bed reduces breast cancer relapse and is more effective in younger patients. [Copyright &y& Elsevier]