Abstract Purpose/Objective(s): Several randomized clinical trials and non-randomized studies have consistently shown that achievement of pathologic complete response (pCR) in the breast with negative axillary nodes is associated with excellent long-term outcomes. NSABP B-511 is a phase III trial aimed to determine if chest wall and regional nodal irradiation (CWRNI) post-op reduces invasive breast cancer recurrence-free interval in patients (pts) with positive axillary lymph nodes (LN) who achieve pCR after neoadjuvant chemotherapy (NAC). However, physicians might be biased towards avoiding enrollment of young patients (≤ 45 years) in this trial. Which in turn, could give way to this population becoming under-represented at the time of determining the standard of care. Our primary objective is to determine if the omission of CWRNI is associated with an increased risk of recurrence in a young patient population. Materials/Methods: Data were obtained from two institutions in South Florida. Patients aged ≤ 45 years, with non-metastatic invasive breast cancer, and positive clinical (LN) involvement, diagnosed between 2010 to 2017 and treated with NAC were identified through retrospective chart review. Disease recurrence including local and distant recurrence data were collected. The Kaplan-Meier survival function was used for plotting patients treated with CWRNI vs no CWRNI and the log-rank test was used to evaluate the recurrence-free survival according to groups. We reported recurrence probabilities at 5 years. Additionally, we also estimated hazard ratios (HRs) of patients treated with CWRNI vs no CWRNI using Cox proportional hazards regression analysis. Results: A total of 154 patients were identified. Median age was 39 years (24-45). Patients were 57% ER+, 33% HER2+, 29% triple negative and 59.1% were stage 3, with only 1 male patient in the cohort. PCR was achieved in 22.1% (34/154) of pts, and CWRNI frequency in these patients was 81.3%. Overall, 79.9% of pts received post-op CWRNI. Recurrence frequency in patients with a pCR who received CWRNI was 4/26 vs 2/6 in pts that did not receive CWRNI. The Kaplan-Meier survival curves indicated an overall probability of recurrence at 5 years of 31.9% (95%CI 3.8% – 51.8%) in patients that did not receive CWRNI vs 27.49% (95%CI 18.42% – 35.56%) in patients that received CWRNI (log rank p=0.55) however, statistical significance was not met. Cox regression indicated that omission of CWRNI was not associated with an increased risk of recurrence (HR 1.3, 95%CI 0.54 – 3.11, p=0.55). In patients that had a pCR after NAC, omission of CWRNI was not associated with an increased risk of recurrence (HR 2.004, 95%CI 0.36 – 10.9, p=0.42). However, the sample size for these analyses was too small to achieve significance. Conclusion: This data highlights the tendency of giving CWRNI to younger patients with clinically node-positive disease at diagnosis regardless of response to NAC. Overall, absolute recurrence in this cohort was very low. Although an absolute number of recurrences favored CWRNI in the setting of pCR, this was not statically significant given the small sample size. Citation Format: Danielle Cerbon, Alex Sanchez-Covarrubias, Brianna Conte, Cristiane Takita, Lora Freedman, Jessica Meshman, Stuart Samuels, Caroline Shermoen, Neha Goel, Ruben Carmona, Lora Wang. Chest-Wall and Nodal Irradiation in Non-Metastatic, Node Positive Breast Cancer Patients with Pathologic Complete Response After Neoadjuvant Chemotherapy and Surgery, in A Retrospective Cohort of Women Aged 45 Years and Younger. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-36.