Long-term results of preoperative hypofractionated chemoradiotherapy for high-risk HER2-positive and triple-negative breast cancer subtypes.

PURPOSE/OBJECTIVE: Concurrent chemoradiotherapy is an established treatment modality for several solid malignancies, whereas its role in breast cancer remains investigational. This study reports the five-year efficacy, safety, and survival outcomes of preoperative concurrent chemoradiotherapy (PCRT) in patients with HER2-positive and triple-negative breast cancer. MATERIALS AND METHODS: This is a prospective single-center pilot study that includes 62 patients with non-metastatic HER2-positive or triple-negative breast cancer treated between 2018 and 2022. Patients received hypo-fractionated radiotherapy (40.5 Gy/15 fractions with a simultaneous integrated boost to 54 Gy to the macroscopic tumor using 18-FDG-PET-CT) delivered concurrently with subtype-specific systemic therapy, followed by surgery. Surgery was performed 4-6 weeks after PCRT. Primary endpoints included pathological complete response (pCR), toxicity, and long-term oncological outcomes. RESULTS: Between September 2018 and August 2022, 62 patients were enrolled (median age 53 years). Tumor subtypes were 28 TN (45%) and 34 HER2 + (55%). 60 patients completed preoperative concurrent chemo-radiotherapy. Breast-conserving surgery was achieved in 68% of cases. Pathologic complete response (pCR, Miller-Payne's Grade 5) was obtained in 60% overall-70% in TN and 52% in HER2 + patients. No grade ≥ 3 late toxicity was observed. A total of 43% of patients experienced G2, 26% G3, and 13.7% G4 cytopenia. Transient asymptomatic declines in left ventricular ejection fraction occurred in 7% of HER2-positive patients and resolved completely during follow-up. Two patients died before surgery, one from chemotherapy-related sepsis and one from causes unrelated to treatment. With a median follow-up of 60.7 months, 5-year locoregional recurrence-free survival was 100%, disease-free survival 95%, distant metastasis-free survival 95%, and overall survival 95%. A total of 2 patients (3%) developed an independent contralateral primary breast tumor during the follow-up; both cases were treated according to standard protocols, and both remain free of disease to date. However, a total of 3 patients experienced distant disease recurrence. Only one death was cancer-related. Cosmetic results were rated as excellent or good in all breast-conserving cases. Out of the 19 patients (32%) who underwent mastectomy, a breast reconstruction was performed in 11 patients. Reconstruction-outcomes favored autologous over heterologous techniques (p = 0.003). No significant correlation was found between pCR and survival. CONCLUSION: Preoperative hypo-fractionated concurrent chemo-radiotherapy demonstrated encouraging long-term local control, survival, and acceptable toxicity in selected patients with HER2-positive and triple-negative breast cancer. Although these findings support the feasibility of this strategy, confirmation in larger prospective randomized studies is warranted.