Abstract Background: Radiation-induced sarcomas (RIS) are rare malignancies comprising only 2.5-5.5% of all sarcomas. As per the Cahan criteria, diagnosis requires histologically proven sarcoma within or around a previously irradiated site. Breast cancer patients are known to have a higher incidence of RIS compared to other primary solid cancers. Following breast irradiation, RIS typically occur after a prolonged latency up to 20 years, although this is often shorter for angiosarcomas. A clear mechanism for RIS development has not yet been elucidated, and prognosis remains poor given limited treatment options. This study aimed to review incidence, risk factors, management, and subsequent oncologic outcomes of breast RIS using 20-year experience at the McGill University Health Centre (MUHC), a large tertiary care centre. Methods: Using our institutional cancer registry database, we identified patients with histologically proven sarcomas of the breast diagnosed between the years 2000 to 2020. We then identified and included patients meeting the Cahan criteria as described above. Patient data including demographics, oncologic treatment of primary breast cancer as well as subsequent sarcoma, and oncologic outcomes were collected from our electronic medical record systems. Descriptive statistics were used to describe patient demographic data. Oncologic outcomes were assessed using the Kaplan Meier method. Results: From 2000 to 2020, we identified 19 patients with breast RIS: 11 angiosarcomas (57.9%), 3 osteosarcomas (15.8%), 2 carcinosarcomas (10.5%), 2 undifferentiated pleomorphic sarcomas (10.5%) and 1 high-grade leiomyosarcoma (5.3%). The median age at RIS diagnosis was 72 years (range 39-82, mean 67) and median latency period for development of RIS was 112 months (range 53-300, mean 120). In terms of secondary treatment, all patients underwent surgery, either total or partial mastectomy (n=14 and n=5, respectively), 3 patients received systemic therapy, and 6 patients received re-irradiation. The median follow-up time was 31 months (range 6-172, mean 48) from diagnosis of RIS. Overall, 5 patients had recurrence at the site of sarcoma and 1 patient developed distant metastases through the study follow-up. The median time to progression was 7 months (range 4-14). The progression-free survival (95% CI) at two years was 56.1 % (37.4-84.4%). At two years follow-up after sarcoma diagnosis, 2 patients were deceased, resulting in an overall survival (95% CI) of 88.9% (75.5-100%). Conclusion: Our 20-year institutional experience confirms that while RIS of the breast remains rare, when managed in a high patient-volume centre, overall survival outcomes appear favorable when salvage is possible. However, a significant proportion of patients still recur locally after maximal treatment, confirming the aggressive nature of this disease and suggesting further follow-up is needed for survival data maturation. Given the rarity of this disease in the context of limited treatment options, patients with RIS should be ideally managed in high-volume centres where multidisciplinary management is available. Citation Format: Vanessa Di Lalla, Marwan Tolba, Farzin Khosrow-Khavar, Ayesha Baig, Carolyn Freeman, Valerie Panet-Raymond. Radiation-induced sarcomas of the breast: A 20-year single-centre experience [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-23.