The impact of inter-cycle treatment delays on 5-year all-cause mortality in early-stage breast cancer: A retrospective cohort study

Abstract

Background: Inter-cycle delays to chemotherapy are often required to manage drug toxicity. The impact of delays on mortality is poorly characterised. This retrospective cohort study examined the association of treatment delay with all-cause mortality in early-stage breast cancer.  Methods: This real-world analytical study included adult women with stage 2 or 3 breast cancer receiving first-line (neo-)adjuvant chemotherapy between 01/01/2014 and 31/12/2015 in England. Inter-cycle delays > 7 days during the treatment period were calculated, and the association of treatment delay with 5-year all-cause mortality was investigated. Survival was compared between patients experiencing treatment delay and those completing treatment to schedule using landmark methodology and Kaplan-Meier (KM) estimator. Cox proportional hazards regression was used to investigate the impact of delay on survival, using inverse probability of treatment weighting to adjust for confounding variables.  Results: 8567 patients were included. 17 % (1448) experienced inter-cycle delay > 7 days during the treatment period. 1120 (13 %) women had died at the end of the 5-year follow up period. Median follow-up time was 5.5 years. Survival probability was significantly lower in patients experiencing treatment delay by KM estimator analysis (p < 0.0001). Cox proportional hazards regression demonstrated a significant positive association between delay and 5-year all-cause mortality (HR 1.33 95 % CI 1.12–1.61, p < 0.001).  Conclusions: This is the largest study of its kind demonstrating an association between treatment delay and all-cause mortality. These findings support interventions to improve toxicity management allowing completion of chemotherapy to schedule where patients experience treatment delay due to treatment-related toxicity or hospital capacity pressures.