Abstract Background An important advantage of neoadjuvant systemic therapy (NST) in breast cancer patients is down-sizing of the primary tumor. However, many patients with T3 tumors are treated with mastectomy regardless of response to NST. In this study, we evaluated predictive characteristics for positive margins and local control in T3 breast cancer patients who underwent breast-conserving therapy (BCT) after NST. Methods This single institution study included all clinical T3 breast cancer patients (determined by contrast-enhanced magnetic resonance imaging [MRI]) who underwent breast conserving surgery (BCS) after NST between 2000-2015. Clinical T3 was defined as a breast tumor >50mm on MRI pre-NST. Patient, tumor and treatment characteristics were recorded, as well as response on MRI and final pathology. The local recurrence probability was estimated with the Kaplan-Meier method. Predictive characteristics for positive margins in patients undergoing BCS were analyzed using Fishers exact test. Results In total, 115 T3 patients were identified. Patient, tumor and MRI findings are presenting in the table. Median tumor size was 60 mm on MRI pre-NST (range 51-120 mm) and 4 mm after NST (range 0-58 mm). Overall pathologic complete response was 19%: 5% in HR+/HER2- patients, 32% in HR-/HER2+ patients and 40% in TN patients. After initial BCS, 73 patients had negative margins (63.5%), 18 focally positive margins (15.7%) and 24 more than focally positive margins (20.9%). Patients with HR+/HER2- tumors (52%) were more likely to have positive margins than patients with HR-/HER2+ and TN tumors (21% and 19%, p=0.002). In addition, positive margins rate was higher in patients with lobular carcinoma compared to patients with ductal carcinoma (57 vs 32%, p=0.031). Presence of non-mass enhancement on pre-NST MRI was predictive for positive margins (52% in patients with and 25% in patients without non-mass enhancement, p=0.003). Of patient with positive margins, 15 underwent radiotherapy with boost, 6 underwent re-excision and 21 underwent mastectomy. Finally, 94/115 patients were treated with BCT (82%). Of these patients, two had a local recurrence after a median follow-up of 6.5 years (6-year local recurrence probability 2.6% (95%-CI 0-7%). Conclusion In this series, BCT after NST was successful in 82% of patients with T3 breast cancer and local control in this group was excellent. The positive margin rate after BCS was higher in patients with HR+ tumors, lobular carcinoma and tumors with non-mass enhancement on MRI pre-NST. BCT should always be considered in T3 cancers after NST. CharacteristicTotal (n=115)Positive margins (focally+ >focally), n=42(%)p-valueHistology 0.031Ductal9229(32) Lobular2313(57) Subtype 0.002HR+/HER2-6132(52) HER2+347(21) TN203(15) MRI morphology of mass pre-NST 0.948Unifocal288(29) Multifocal4012(33) Multicentric134(31) Only non-mass enhancement34 MRI non-mass enhancement before NST 0.003Absent6516(25) Present5026(52) MRI response after NST 0.952rCR5218(35) non-rCR6221(38) Missing1 Citation Format: van der Noordaa ME, Vrancken Peeters M-JM, Ioan I, Loo CE, van Urk J, van Werkhoven E, Voorthuis R, Wiersma T, Groen E, Rutgers ET, van Duijnhoven FH. Breast conserving therapy after neoadjuvant systemic therapy in patients with T3 breast cancer is feasible [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-13-02.