Impact of Neoadjuvant Chemotherapy Administration Time of Day on Pathological Response in Patients with Early...

Background: Triple-negative breast cancer (TNBC) is associated with poor prognosis, highlighting the need for innovative therapeutic strategies. Chronomodulated chemotherapy yielded improved efficacy and tolerability in several malignancies; however, evidence in breast cancer remains limited. This study investigated the association between the time of day of administration (ToDA) of neoadjuvant chemotherapy (NAC) and clinical outcomes in patients with TNBC treated in a day hospital setting. Methods: This retrospective cohort included patients treated at Saint-Louis Hospital with neoadjuvant dose-dense, dose-intense cyclophosphamide-epirubicin followed by weekly paclitaxel. Infusion start times of each chemotherapy agent were systematically recorded. The primary endpoint was pathological complete response (pCR; Residual Cancer Burden [RCB] = 0). Secondary endpoints included RCB classes, early metabolic response, treatment tolerance, and 36-month event-free survival (EFS). Patients were classified into early or late infusion groups using multiple ToDA cut-offs, and cosine-based analyses were performed. Results: Ninety-four patients (median age 51 years) received NAC between 9:00 and 17:40 which aligns with the day hospital unit's opening hours. With a median follow-up of 39.9 months, the pCR rate was 48.9%. No significant differences were observed between early and late infusion groups for any endpoint, regardless of ToDA cut-off or analytical approach. Conclusions: This first chronotherapeutic study in patients with early TNBC showed no association between ToDA of NAC administered between 9:00 and 17:40 and histological response or EFS. Although limited by sample size and the restricted infusion time window, our study provides novel data and methodological insights supporting further investigation of chronotherapy in patients with breast cancer.