ESTRO 2025 - Abstract Book

S607

Clinical - Breast

ESTRO 2025

Compared to mastectomy alone, no differences in OS were observed for patients treated with BCS+RT (unadjusted HR 1.12, 95% CI 0.89–1.40), while poorer OS was noted in patients treated with mastectomy+RT (unadjusted HR 2.27, 95% CI 1.83–2.82). Conclusion: Young BRCA mutation carriers treated with BCS+RT achieved similar OS to those treated with mastectomy alone, despite a higher incidence of LorC BC. Patients treated with mastectomy+RT exhibited a comparable incidence of LorC BC but poorer OS, suggesting the role of stage at diagnosis in determining survival outcomes. These findings support personalised treatment approaches that account for patient preferences and oncological safety. References: [1] Wan Q, Su L, Ouyang T, et al. Comparison of Survival After Breast-Conserving Therapy vs Mastectomy Among Patients With or Without the BRCA1/2 Variant in a Large Series of Unselected Chinese Patients With Breast Cancer. JAMA Netw Open. 2021 Apr 1;4(4):e216259. [2] Wanis KN, Kuerer HM, Sun SX, et al. Clinical Outcomes for BRCA Pathogenic Variant Carriers With Breast Cancer Undergoing Breast Conservation. JAMA Netw Open. 2024 Jun 3;7(6):e2418486. [3] Lambertini M, Blondeaux E, Agostinetto E, et al. Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study. JAMA. 2024 Jan 2;331(1):49-59. Keywords: BRCA, Survival Outcomes, Breast Conserving Therapy Digital Poster DNA profiling assessment in early-stage breast cancer after neoadjuvant Cyberknife® radiotherapy -The CRYSTAL study (NCT04679454) Simona Pessina 1 , Chiara Zanetti 1 , Maria Cristina Leonardi 2 , Maria Alessia Zerella 2 , Mattia Zaffaroni 2 , Maria Giulia Vincini 2 , Giuseppe Ronci 2 , Samantha Dicuonzo 2 , Damaris Patricia Rojas 2 , Anna Morra 2 , Cristiana Fodor 2 , Elena Rondi 2 , Silvia Penco 3 , Viviana Enrica Galimberti 4 , Giuseppe Renne 1 , Federica Cattani 2 , Elisa De Camilli 1 , Barbara Alicja Jereczek-Fossa 2,5 , Federica Conversano 1 1 Pathology division, European Institute of Oncology IRCCS, Milan, Italy. 2 Radiotherapy Division, European Institute of Oncology IRCCS, Milan, Italy. 3 Radiology Division, European Institute of Oncology IRCCS, Milan, Italy. 4 Senology department, European Institute of Oncology IRCCS, Milan, Italy. 5 University of Milan, university of Milan, Milan, Italy Purpose/Objective: Radiotherapy induces various structural DNA lesions, particularly double-strand breaks (DSBs). DSBs recruit the 53BP1 protein to chromatin, where it interacts with methylated histone H3 Lys 79 in a γH2A.X-dependent manner, signaling DNA damage and chromatin alterations. CRYSTAL trial (NCT04679454) is a monocentric phase I/II, single arm, and open-label study that enrolls patients to receive an ablative dose (18–24 Gy) to the tumor with CyberKnife® at least 4 weeks before the surgery. In this proof-of-concept study, we examined the early biological effects of neoadjuvant CyberKnife® radiotherapy in 14 patients with early-stage breast cancer. Material/Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples were used to assess biological markers. One patient was excluded due to the absence of residual tumor. In addition to standard histopathological analyses, the Residual Tumor Burden (RTB) index and various immunohistochemistry (IHC) markers (anti-caspase-3, CAFs, CD4, CD8, CD20, FAP, HIF-1α, PD-L1, TILs) were evaluated. DNA was extracted using the Maxwell Platform, and DNA integrity was assessed with TapeStation, providing a DNA Integrity Number (DIN) on a scale of 1–10. Immunofluorescence assays detected γH2A.X and 53BP1 foci, markers of DSBs, which were analyzed using Metafer 4 Metacyte v3.14.143 software. 4048