ESTRO 2025 - Abstract Book

S469

Clinical - Breast

ESTRO 2025

HER2+ breast cancer with residual disease after neoadjuvant chemotherapy. 2 Both ICIs and T-DM1 are associated with a risk of drug-induced pneumonitis. Radiotherapy is also a standard of care treatment for localized breast cancer, which carries an independent risk of pneumonitis. The potential interaction between ICIs, T-DM1 and radiotherapy in modulating the risk of pneumonitis is uncertain. 3,4 Material/Methods: This is a retrospective study. All patients with localized HER2+ or TN breast cancer who were treated with radiotherapy at our institution from 2019-2024 were assessed. Pneumonitis was assessed for 1 year following completion of radiotherapy. The association of the outcomes (pneumonitis, mortality) with patient/clinical factors of interest were examined using logistic regression and survival analysis. Results: 874 eligible patients were included in the analysis. Of these, 533 were HER2+ and 341 were TN. The rate of Grade ≥2 pneumonitis (G2P) was 3.1% in the entire cohort: 4.0% of HER2+ patients, and 1.8% of TN patients. The median time from completion of radiotherapy to G2P was 1.7 months (IQR 0.8-2.9 months). There was no significant difference in the rates of G2P between the 5, 15/16, or 25 fraction radiotherapy regimens (p=0.09). On UVA, there was a higher probability of G2P in patients who received locoregional vs. breast only radiotherapy, although this did not meet statistical significance on MVA (OR=0.35, 95% CI 0.08-1.53, p=0.74). There was no significant increase in G2P between patients who received perioperative pembrolizumab vs. patients who did not (OR=0.76, 95% CI=0.10-5.71, p=0.79). On UVA, there was a significant association between adjuvant T-DM1 and the development of G2P; this was also significant on MVA (OR=6.88, 95% CI=2.66-17.80, p<0.01). Conclusion: The overall probability of G2P in patients receiving radiotherapy for localized TN or HER2+ breast cancer was low, with a 3.1% incidence of G2P. The rate did not increase with hypofractionated RT, nor with the addition of perioperative pembrolizumab. Adjuvant T-DM1 was associated with a significantly increased risk of G2P. Further work will explore additional clinical, systemic therapy, dosimetric, and radiomic predictors of G2P in the high-risk group of patients who received T-DM1. References: 1. Schmid P et al. Pembrolizumab for Early Triple-Negative Breast Cancer. New England Journal of Medicine. 2020;382(9). 2. von Minckwitz G et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019;380(7):617-628. 3. Verma S et al. Immunotherapy and Radiation Therapy Sequencing in Breast Cancer: A Systematic Review. International Journal of Radiation Oncology*Biology*Physics. Published online 2024. 4. Meattini I et al. International multidisciplinary consensus on the integration of radiotherapy with new systemic treatments for breast cancer: European Society for Radiotherapy and Oncology (ESTRO)-endorsed recommendations. Lancet Oncol. 2024;25(2):e73-e83. Keywords: pneumonitis, breast cancer, radiation

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Digital Poster Proton Beam Hypofractionated Reirradiation in Locoregionally Recurrent Breast Cancer: Early Toxicity Outcomes Samantha Dicuonzo 1 , Floriana Pansini 1 , Stefania Comi 1 , Marco Liotta 1 , Federica Cattani 1 , Damaris Patricia Rojas 1 , Marianna Alessandra Gerardi 1 , Maria Cristina Leonardi 1 , Giovanni Carlo Mazzola 1 , Annamaria Ferrari 1 , Luca Bergamaschi 1 , Anna Morra 1 , Maria Alessia Zerella 1 , Giulia Marvaso 1,2 , Stefania Volpe 1,2 , Cristiana Fodor 1 , Ilaria