ESTRO 2025 - Abstract Book

S614

Clinical - Breast

ESTRO 2025

Regarding toxicities of special interest for T-DXd, G2 interstitial lung disease (ILD) or G2-3 pneumonitis were observed in four cases in the RT group (12.1%) and eight cases in the no-RT group (9.4%). No cases of radionecrosis were reported among the 17 patients treated with intracranial RT. Conclusion: Our preliminary findings are encouraging, suggesting that the combination of T-DXd and concurrent RT does not increase the risk of severe acute toxicity. References: 1. Cortés J et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Feb 24;386(8):724-734. 2. Modi S et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. 3. Palma DA et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: Long-term results of the SABR-COMET Phase II randomized trial. J Clin Oncol 2020;38:2830–8. Keywords: Trastuzumab Deruxtecan, Radiotherapy, Integration Digital Poster High-penetrance genetic mutations in breast cancer patients: radiotherapy outcomes and toxicities Horatiu-Adrian Ciliboaie 1 , Alexandru Tipcu 1 , Nicoleta Antone 2 , Ioana Brie 1 , Andreea Catana 3 , Vlad Coltea 1 , Andrei Man 1 , Marius Maxin 2 , Adrian Trifa 3 , Andrada Turcas 1 , Daniela Martin 2 1 Radiotherapy, The Oncology Institute “Prof. Dr. Ion Chiricuta”, Cluj-Napoca, Romania. 2 Breast Tumor Center, The Oncology Institute “Prof. Dr. Ion Chiricuta”, Cluj-Napoca, Romania. 3 Oncogenetics, The Oncology Institute “Prof. Dr. Ion Chiricuta”, Cluj-Napoca, Romania Purpose/Objective: Breast cancer patients with high-penetrance genetic mutations often face unique therapeutic challenges. Radiotherapy (RT) remains a critical component of breast cancer treatment, but its efficacy and safety in patients with genetic predispositions are subjects of ongoing research. This study explores the impact of RT on patients harbouring high-risk mutations, focusing on treatment outcomes and balancing therapeutic benefits against genetic predisposition-related risks. Material/Methods: This retrospective study included breast cancer patients treated at a tertiary cancer institute who underwent genetic testing for high-penetrance mutations. We selected patients who received radiotherapy and evaluated relapse rates and secondary malignancies based on their genetic status. Radiotherapy protocols included 2D, 3D, IMRT, VMAT and helical tomotherapy, with doses and fractionation adjusted per institutional standards. Statistical analyses included chi-square and Fisher’s exact tests for categorical variables, Mann-Whitney U tests for non-parametric comparisons, and Spearman correlation tests for assessing relationships between variables. Results: A total of 132 patients were included in this study. The incidence of relapse was higher in patients with pathogenic genetic mutations compared to those with no mutations or variants of uncertain significance (VUS), with 69.2% of relapses occurring in the first group. There was a significant difference in relapse rates (p = 0.02) for pathogenic mutations, with an odds ratio (OR) of 3.977 (95% CI: 1.156–13.684). Eighty-nine percent of relapses occurred in patients with high-penetrance genetic syndromes compared to those with moderate (11%) or low penetrance genetic mutations (0%), with a significant difference (p = 0.035). No significant differences were observed between 4125