2771 - Radiation Therapy for Breast Cancer in Patients with Li-Fraumeni Syndrome (LFS): A Single Institution Cohort Study

Purpose/Objective(s): 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 radiation therapy 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 to determine whether radiotherapy negatively impacted clinical outcomes.

Materials/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. Primary endpoint was overall survival.

Results: From 1989 to 2025, we identified 39 female LFS breast cancer patients who met our inclusion criteria. Median age at diagnosis was 29 years (range 24-44). Of them, 61.5% had a family history of cancer suggestive of LFS and the syndrome was already known before the breast cancer diagnosis in 15 patients. 38.5% had tumoral HER2 amplification. 66.7% received a total mastectomy and 33.3% received a partial mastectomy. 21 patients (53.8%) received radiotherapy as a part of their treatment strategy. The median follow up was 95 months (range 26-157). Overall survival (OS) at 5 and 10 years was 82.5% (95% CI: 70.7-96.3%) and 64.0% (95% CI: 48.8-84.0%) respectively.

No case of radiation-induced sarcomas after breast adjuvant irradiation was observed during the follow-up period. In the radiotherapy group, 4 patients (19%) later developed a malignancy within the irradiated field. In univariate analysis, radiotherapy was not significantly associated with overall survival (HR=0.55, 95% CI: 0.19-1.66, p=0.28), with median OS of 197 months in the RT group versus 123 months in the no-RT group. Radiotherapy showed no significant impact on cancer-specific survival (p=0.83), metastasis-free survival (p=0.54), locoregional recurrence-free survival (p=0.34), or contralateral breast cancer incidence (HR=0.77, 95% CI: 0.21-2.91, p=0.69).

Surgery type, chemotherapy administration, T stage (Tis-T1-T2 vs T3-T4), N stage (N0 vs N+), and receptor status (TNBC vs HER2+ vs HR+/HER2-) showed no significant association with overall survival in univariate analyses (p>0.05 for all comparisons).

Conclusion: The incidence of radiation-induced sarcomas was lower than anticipated. No significant differences in overall survival or other clinically relevant outcomes were observed between patients who underwent radiotherapy and those who did not. Further studies with larger cohorts and extended follow-up are required to validate these findings.