Partial breast irradiation followed by neoadjuvant immunochemotherapy in early TNBC.

e12649 Background: Neoadjuvant immunochemotherapy (NAICT) incorporating immune checkpoint blockade has become standard for triple-negative breast cancer (TNBC). However, a substantial proportion of patients, particularly those with immune-cold tumor microenvironment (TME), fail to achieve pathological complete response (pCR) despite pembrolizumab treatment, highlighting the need for strategies to enhance antitumor immunity. Emerging evidence suggests that radiotherapy can favorably modulate TME and augment immune checkpoint blockade. We retrospectively evaluated outcome of early TNBC patients treated with partial breast irradiation (PBI) prior to NAICT with pembrolizumab. Methods: Patients with TNBC who received PBI to the primary tumor before NAICT between July 2022 and June 2025 were retrospectively analyzed. Eligible criteria included age ≥ 20 years, ER and PR expression < 1%, HER2-negative invasive carcinoma, and clinical stage II-III disease (cT2-4N0-3 or cT1N1-3). All patients received single-fraction PBI (8 Gy), followed by neoadjuvant NAICT with four cycles of carboplatin every 3 weeks plus paclitaxel weekly, followed by four cycles of anthracycline-based chemotherapy every 3 weeks. Pembrolizumab was administered concurrently every 3 weeks for a total of eight cycles. For comparison, 186 patients who did not receive PBI were included in the analysis. Results: 21 patients completed PBI and NAICT followed by curative surgery. Median age was 43 years (range, 29-71). Overall, 95.2% had cT2-4 disease, 47.6% had cN2-3 disease, and 66.7% had grade III tumors. The overall pCR rate was 71.4% (15/21). Among the patients with immune-cold TME, defined as stromal tumor-infiltrating lymphocytes (sTIL) < 30% and PD-L1 combined positive score (CPS) < 10, the pCR rate was 64.7% (11/17). Among patients with pCR, 63.6% (7/11) had grade III tumors, 81.8% (9/11) had cT2-4 disease, and 54.5% (6/11) had cN2-3 disease. With short-term follow-up, no patient with pCR experienced disease recurrence. In the comparison group of 186 patients without PBI, the pCR rate was 66.1% (123/186). No new or notable adverse effects were identified in patients who received PBI. Conclusions: A single dose of PBI 8Gy to primary tumor before NAICT yielded a promising pCR rate, supporting the hypothesis that radiotherapy modulates the TME and enhances local antitumor immunity. This approach was particularly beneficial for patients with immune-cold TME. A prospective phase II study (NCT07011823) exclusively enrolling patients with immune-cold TME is underway to validate these findings and define the clinical role of PBI prior to NAICT in early TNBC.