Concurrent Versus Sequential Adjuvant Capecitabine-Based Chemoradiation in Residual Triple-Negative Breast Cancer After Neoadjuvant-Chemotherapy: A Multicenter Comparative Study

Purpose: Given the aggressive nature and poor prognosis of triple-negative breast cancer (TNBC), adjuvant capecitabine has been the standard therapy for residual disease after preoperative systemic therapy (PST). However, the optimal sequence of postoperative radiation therapy (RT) and capecitabine remains unclear. This study evaluated the efficacy and safety of concurrent RT and capecitabine (RT+CAP) versus sequential RT followed by capecitabine (RT→CAP) in patients with residual TNBC after PST. Methods and Materials: In this multicenter retrospective study, data from 491 patients treated at 14 tertiary hospitals were analyzed. The patients received either postoperative RT→CAP (n = 255) or RT+CAP (n = 236). Survival outcomes were analyzed using the Kaplan-Meier method, and multivariable Cox regression was used to adjust for potential confounders. Results: There were no significant differences in the baseline characteristics between the 2 groups. With a median follow-up of 41.8 months, the 4-year rates of disease-free survival (DFS) and overall survival (OS) were 68.8% and 82.4%, respectively. The RT+CAP group demonstrated improvements in DFS (74.6% vs 63.7%, P =.045) and OS (86.8% vs 78.3%, P =.006) compared with the RT→CAP group. Specifically, RT+CAP showed superior DFS and OS outcomes in patients with a low disease burden (ypT0-1, ypN0/axillar level I only, or Ki67 <15%). Additionally, the incidence of ≥grade 2 toxicities and discontinuation of capecitabine because of toxicity did not differ, indicating that RT+CAP was well tolerated. Conclusions: RT+CAP offers improvements in oncologic outcomes without an increase in adverse events compared with RT→CAP, suggesting it is a promising treatment option for patients with residual TNBC after PST.