Abstract PS2-05-29: Feasibility and outcomes of premastectomy radiation therapy in locally advanced breast cancer

Abstract Introduction: There is growing evidence to support the oncologic feasibility of pre-mastectomy radiotherapy (PreM-RT) to allow immediate breast reconstruction (IBR). Most trials excluded patients with locally advanced breast cancer (LABC), cT3-4N0-3M0. Generally, LABC patients are recommended trimodality therapy with neoadjuvant chemotherapy (NAC) followed by surgery, and ultimately radiation therapy (RT). Patients who undergo mastectomy are recommended delayed reconstruction to decrease postoperative complications and prevent RT delays. We aimed to assess the feasibility of PreM-RT followed by mastectomy with IBR for LABC. Methods: This was a prospective, single arm, feasibility trial. Women age ≥18 with cT3-T4N0-N3M0 breast cancer with partial or complete response to NAC by RECIST criteria, and desired IBR were enrolled beginning 01/2022. All patients received NAC and PreM-RT. The primary endpoint was postoperative wound complication rate. Secondary endpoints reported here include physician reported RT toxicities at baseline and weekly during PreM-RT using the NCI CTCAE v5, as well as patient reported outcomes at baseline, during RT, preoperatively, and postoperatively using the complementary PRO-CTCAE. Results: Among 27 patients, median (IQR) age was 42 (37-57) years (1 Asian [3.8%], 5 Black [19], 16 White [62%], and 6 Hispanic [24%]). 48% (13/27) were ER+/HER2-, 30% (8/27) were ER-/HER2-, and 52% (14/27) had inflammatory breast cancer (IBC). 25/27 patients completed PreM-RT and surgery at this time, and all had autologous reconstruction. Median (IQR) time from end of NAC to start of RT was 38 days (32-42); median (IQR) time from end of RT to surgery was 34 days (30-40.5). Dosing of PreM-RT was 50 Gy in 25 daily 2-Gy fractions over 5-6 weeks (24/25, 96%) or 42.56 Gy in 16 daily 2.66-Gy fractions over 3-4 weeks (1/25, 4%). Most prevalent physician reported RT toxicities were dermatitis (25/25, 100%) and fatigue (25/25, 100%), with the majority grade 1-2 toxicities (Table). Grade 3-4 toxicities were only reported for dermatitis (7/25, 28%), fatigue (3/25, 12%), and breast lymphedema (1/2, 50%). The most common patient reported RT toxicities were pain, fatigue, skin breakdown, and breast enlargement (Table). 12% (3/25) of patients developed postoperative complications. 2 had flap skin necrosis; 1 required bedside debridement and 1 resolved without intervention by postoperative month 3. The third had a delayed hematoma at postoperative week 5 after resuming therapeutic anticoagulation and required washout. Conclusion: PreM-RT followed by mastectomy with IBR for patients with LABC appears safe, with postoperative complication rates lower than reported for delayed autologous reconstruction (∼30%). This is among the first reports of PreM-RT in IBC patients. Patients tolerated PreM-RT with no surgical delay, and physician/patient reported RT toxicities mirror the postmastectomy RT population. Citation Format: R. Kiernan, V. Sevilimedu, A. Xu, M. Corriddi, L. Hor, A. Pellecchia, M. Morrow, A. Khan, A. Tadros. Feasibility and outcomes of premastectomy radiation therapy in locally advanced breast cance [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-05-29.