Abstract PS2-04-21: Impact of Pre-Neoadjuvant Radioactive Iodine Seed Marking on Pathological Complete Response and Survival in Breast Cancer Patients

Abstract Background: Pre-neoadjuvant marking of the primary tumor and biopsy-confirmed metastatic axillary lymph nodes is critical for enabling de-escalation of surgery, facilitating the retrieval of the lesion and assessing treatment response. Radioactive iodine-125 (125I) seeds are commonly used for localization. However, potential radiobiological effects from 125I seeds could confound pathological assessment of treatment response, possibly leading to suboptimal adjuvant therapy decisions and compromised long-term prognosis. We evaluated the pathological and prognostic impact of 125I seed marking before Neoadjuvant therapy (NAT) and employed peripheral blood profiling to explore immune-related mechanisms. Methods: We conducted a retrospective analysis of 1,594 cT1-4N1-3M0 breast cancer patients who received NAT treatment at Shandong Cancer Hospital and Institute during 2017 to 2024. 216 patients with and 432 without 125I seed marking were included after a 1:2 propensity score match. The primary endpoint was pCR; the secondary was invasive disease-free survival (iDFS). To investigate immune modulation, peripheral blood samples from triple-negative breast cancer (TNBC) patients were collected at baseline as well as after second NAT cycle for flow cytometry (CD3+/CD4+/CD8+/CD16+/CD19+). Results: The 125I marked group achieved significantly higher pCR rates than the without 125I seed marked group: total pCR (55% vs. 46%, P = 0.030), breast pCR (63% vs. 53%, P=0.016), and axillary pCR (71% vs. 60%, P = 0.009). Subgroup analyses highlighted the greatest benefits in TNBC (tpCR:59% vs. 39%, P = 0.033) and hormone receptor-positive/HER2-negative (HR+/HER2−) subtypes (tpCR:26% vs. 8%, P = 0.028). After a median follow-up of 36.7 months, 50 iDFS events were recorded. the 3-year iDFS was significantly higher in the 125I seed marked group (96% vs. 90%; P = 0.018). Kaplan-Meier survival analysis based on pCR achievement showed that patients achieved pCR in both groups had a lower risk of recurrence compared to non-pCR patients (125I seed marked group: 99% vs. 83%, P = 0.003; without 125I seed marked group: 96% vs. 85%, P = 0.021).Importantly, within the pCR patients, Both groups exhibited similarly favorable prognosis, regardless of 125I seed marked (99% vs. 96%, P = 0.875).Flow cytometry showed increased CD8+ T cells and CD16+ NK cells, and reduced CD4+ T cells in 125I marked patients. Conclusions: 125I seed marking before NAT improves pCR rates, especially in TNBC and HR+/HER2−subtypes. As pCR is strongly associated with improved iDFS, this increase in pCR likely translates into survival benefit. Flow cytometry suggests that localized radiation at the 125I seed marking may promote CD4+ T cell trafficking and Treg exhaustion, thereby enhancing effector and cytotoxic immune responses. These findings support the immunologic relevance of seed localization and provide a rationale for future immunotherapy combinations. Citation Format: Y. Geng, Q. Zhang, Z. Shi, Z. Bi, Y. Wang, P. Qiu. Impact of Pre-Neoadjuvant Radioactive Iodine Seed Marking on Pathological Complete Response and Survival in Breast Cancer Patients [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 PS2-04-21.