Abstract Background: Li-Fraumeni syndrome (LFS), caused by monoallelic germline pathogenic variant (PV) in TP53 gene, causes an elevated risk of developing certain cancers, mainly early onset breast cancer, sarcoma and brain tumors. While LFS patients are believed to be at an increased risk for radiation-induced sarcomas, only a few retrospective studies have been published studying the impact of radiationtherapy in the treatment of breast cancer among these patients. This study reviews the data concerning LFS patients treated at the Institut Curie with adjuvant radiation therapy for localized breast cancer. Methods: A retrospective study was conducted on female breast cancer patients with confirmed TP53 PV treated at the Institut Curie. Data concerning patients’ characteristics, treatments received, radiotherapy if received, rates of recurrences, rates of radiation induced sarcomas (RIS) and patient outcomes were collected. Results: From 1989 to 2024, we identified 47 female LFS breast cancer patients who met our inclusion criteria. Median age at diagnosis was 31 years (range 18-72). Of them, 76.6% had a family history of cancer suggestive of LFS. 31.9% had tumoral HER2 amplification. 51.1% received a mastectomy and 31.9% received a lumpectomy. 23 patients (48.9%) received radiotherapy as a part of their treatment strategy. The median follow up was 111 months (range 7-413). Among patients who received radiotherapy, 3 (13%) had a known diagnosis of LFS prior to treatment. No case of radiation-induced sarcomas was observed during the follow-up period. In the radiotherapy group, 5 patients (21.7%) later developed a malignancy within the irradiated field. At 10 years post-diagnosis, overall survival did not differ significantly between patients who received radiotherapy and those who did not (58.2% 95%CI: 36.8-91.9 vs. 80.1% 95%CI: 64.2-100). Similarly, there was no significant difference in loco regional recurrence-free survival (95.2% 95%CI: 86.6-100 vs. 74.0% 95%CI: 54.8-99.9) or in survival free from subsequent non-breast cancers (59.6% 95%CI: 36.5-97.2 vs. 67.2% 95%CI: 49.8-90.7). Univariate analysis did not find any correlation between hormonal status, grade, surgical technique, stage, use or non-use of radiotherapy and overall survival, cancer-specific survival, loco regional recurrence-free survival, metastasis-free survival. Conclusion: The incidence of radiation-induced sarcomas and local recurrences in LFS breast cancer patients was lower than anticipated. Further studies with larger cohorts and extended follow-up are required to validate these findings. Citation Format: A. A. Shrebati, P. Loap, E. Mouret-Fourme, K. Cao, M. Belotti, D. Stoppa-Lyonnet, Y. Kirova. Radiation therapy for breast cancer in patients with Li-Fraumeni syndrome (LFS): a single institution cohort study 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 PS1-03-06.
Shrebati et al. (Tue,) studied this question.