Purpose/Objective(s): The role of PMRT in patients with T1-2N1 breast cancer is controversial. Retrospective reviews reported locoregional recurrence rates of 6-13%, arguing for a very small or no survival benefit of PMRT. However, subset analysis of the Danish PMRT trials showed a 9% OS benefit in patients with 1-3 positive nodes. The meta-analysis by EBCTCG reported a 4.4% OS benefit of PMRT at 15 years. Should all node-positive patients receive PMRT? In this study, we sought to examine the relationship of PMRT and OS and to identify potential subsets of T1-2N1 patients who are least likely to derive benefit from PMRT. Materials/Methods: We analyzed the SEER registry of breast cancer patients diagnosed between 1998 and 2006. We identified 20,882 women with T1-2N1M0 breast cancer who were treated with mastectomy. Among those, 4498 patients received PMRT. Median follow-up was 43 months (range, 4-107 months). Pearson chi-square test was used to compare characteristics of the PMRT and no PMRT groups. OS rates were calculated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox regression model, and included variables tumor size, grade, nodal ratio, and PMRT use. Results: PMRT use was associated with previously reported adverse clinicopathologic factors, including large tumor size, high grade, multiple positive nodes, and nodal ratio . = 0.2 (p \ 0.001). Kaplan-Meier analysis showed OS was better in the PMRT group, compared to no PMRT (8-yr OS of 77% vs. 74%, log-rank p = 0.002). In multivariate analysis, we identified PMRT (HR = 0.73, 95% CI 0.66-0.80), T . 2 cm (HR = 1.85, 95% CI 1.70-2.01), high grade (HR = 1.71, 95% CI 1.59-1.85) and nodal ratio . 0.2 (HR = 1.51, 95% CI 1.39-1.64) as significant prognostic factors (all p \ 0.001). In patients with low risk features such as grade I, T1, nodal ratio \ = 0.15, or grade I and T1 and nodal ratio \ = 0.2, OS was not different between PMRT and no PMRT (p = 0.1, 0.1, 0.5, and 0.4, respectively). Conclusions: Our study suggests that PMRT is associated with improvement in OS in patients with T1-2N1 breast cancer. However, PMRT does not seem to benefit those with very low risk features, including grade I tumors, T1 tumors, nodal ratio \ 0.15, or grade I and T1 and nodal ratio \ = 0.2. Our findings may be helpful in developing nomograms for clinical decision making. The ongoing randomized phase III SUPREMO trial will help better define the indications and treatment volume of PMRT.