In press. Effect of chemotherapy timing in triple-negative breast cancer: a real-world evidence study

Purpose: Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous malignancy with poor prognosis. The optimal timing of chemotherapy—neoadjuvant (NACT) versus adjuvant (ACT)—remains controversial. This study assessed real-world outcomes in non-metastatic TNBC patients according to chemotherapy timing. Methods: This retrospective study (2008–2023) evaluated the impact of chemotherapy timing on overall survival (OS) and event-free survival (EFS) in a cohort of 711 patients. Propensity score (PS) matching with preoperative variables was used to adjust for baseline imbalances, and Cox regression models were applied to account for treatment-related variables. Results: NACT was administered to 525 patients (73.8%), with a 37.3% pathological complete response (pCR) rate. PS matching yielded 177 patient pairs; tumor stage, age and histologic grade remained unbalanced. In the unadjusted analysis, NACT was associated with worse OS (HR 1.56, 95% CI1.08–2.25, p = 0.018). However, multivariate analysis adjusting for unmatched and postoperative variables showed a potential benefit of NACT for OS (HR 0.53, 95% CI 0.07–4.13, p = 0.545) and EFS (HR 0.94, 95% CI 0.21–4.17, p = 0.932). Tumor stage acted as an effect modifier, and stratified analyses revealed that NACT was superior to ACT in patients with advanced-stage disease who achieved pCR (HR 0.22, 95% CI 0.07–0.7, p < 0.010). Conclusions: In our TNBC cohort, chemotherapy timing significantly influenced OS and EFS, particularly in relation to initial tumor stage and pCR status. NACT was more beneficial than ACT in patients with advanced disease who achieve pCR, underscoring its role in both prognostic stratification and therapeutic decision-making.