Abstract PS1-07-19: Comparing Utilization and Survival Outcomes of Post-mastectomy Radiation Therapy in Invasive Lobular versus Ductal Carcinoma: A National Cancer Database Analysis

Abstract Background: Post-mastectomy radiation therapy (PMRT) can improve locoregional control and overall survival in patients with invasive breast cancer, particularly those with high-risk features such as ≥4 positive lymph nodes or T3-T4 tumors. However, data on the utilization and effectiveness of PMRT across different histological subtypes remain limited. Invasive lobular carcinoma (ILC), the second most common histologic subtype of breast cancer, differs from invasive ductal carcinoma (IDC) in its features and clinical outcomes, with more hormone receptor positive status and lower grade, but typically higher stage at presentation, higher risk of positive surgical margins, and propensity for late recurrences. Given the unique features of ILC, including a characteristic diffuse growth pattern, we hypothesized that more patients with ILC would receive PMRT, and, that the use of PMRT might have relatively greater survival benefit in patients with ILC than those with IDC. Methods: We used the National Cancer Database (NCDB) to identify patients diagnosed with pathologic stage I-III breast cancer between 2010 and 2020 who underwent mastectomy, with or without adjuvant radiation therapy. Patients who received neoadjuvant radiotherapy or intraoperative radiotherapy were excluded. We considered the following criteria to be an indication for PMRT: T3 tumor with age <50 years, T3 tumor with lymphovascular invasion (LVI), N2 or greater nodal involvement, positive surgical margins, tumor grade 3 with LVI, T1-2N2 category with tumor grade 3 or LVI. PMRT utilization was compared between ILC and IDC using chi-square analyses, and stratified by age, tumor stage, and receptor subtype. Multivariable Cox proportional hazards models were used to evaluate the association between PMRT and overall survival (OS), adjusting for age, T category, N category, hormone receptor/HER2 subtype, and tumor grade in ILC and IDC cohorts; a test of interaction between histology and PMRT was included to assess differential benefit. Results: Of 1,774,249 patients with stage I-III breast cancer in the NCDB, 472,499 patients met our eligibility criteria, of whom 94,359 (20%) had ILC and 378,140 (80%) had IDC. In total, 32% patients received PMRT, with significantly higher utilization rates in patients with ILC compared to IDC (37% vs 30%, p<0.001). In stratified analysis, ILC patients had more PMRT across receptor subtypes and age groups, but only within the stage III cohort, suggesting that higher stage is driving increased PMRT in ILC patients. Among patients meeting the indication for PMRT, those who received radiation had improved overall 5-year survival than those who did not (log-rank p<0.001). In separate multivariable models within the subgroups of ILC and IDC, the adjusted hazard ratio for death within 5-years in ILC patients was 0.66 (95% CI: 0.62-0.70, p<0.001) in those receiving PMRT compared to those who did not, while in IDC patients it was 0.74 (95% CI: 0.72-0.76, p<0.001), with a significant test of interaction (p=0.01), suggesting differential survival benefit by histologic subtype. Conclusion: PMRT is more frequently utilized in patients with ILC than those with IDC. While PMRT is associated with improved overall survival in both subtypes, the relative benefit of PMRT appears greater in patients with ILC than IDC, perhaps reflecting the greater risk of occult residual disease in those with diffusely growing tumors like ILC. These findings highlight the importance of considering histologic subtype when evaluating the role of PMRT and the need to tailor radiation strategies in lobular breast cancer. Citation Format: Y. Chen, A. Shui, C. Lee, A. Vertido, M. Kaur, J. Moya, E. Abeles, A. Quirarte, J. A. Mouabbi, N. Prionas, R. Mukhtar. Comparing Utilization and Survival Outcomes of Post-mastectomy Radiation Therapy in Invasive Lobular versus Ductal Carcinoma: A National Cancer Database Analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-07-19.