Impact of timeliness of adjuvant chemotherapy and radiotherapy on the outcomes of breast cancer; a pooled analysis of three clinical trials

Objective: To assess the impact of delay in initiation of adjuvant chemotherapy and/or radiotherapy on the outcomes of breast cancer patients referred for adjuvant treatment. Methods: This is a pooled analysis of patient-level data of 3390 breast cancer patients referred for adjuvant chemotherapy in three clinical trials. Overall and relapse-free survivals were assessed according to surgery to chemotherapy interval through Kaplan-Meier analysis. Likewise, among patients who received adjuvant radiotherapy, relapse-free survival was assessed according to surgery to radiotherapy interval through Kaplan-Meier analysis. Univariate and Multivariate analysis of factors affecting overall and relapse-free survival was then conducted through Cox regression analysis. Results: Kaplan-Meier analysis of overall survival according to surgery to chemotherapy interval (< vs. > 6 weeks) was conducted. When stratified by the hormone receptor status, the longer interval was associated with worse overall survival in hormone receptor-negative patients (P = 0.006); while it was not associated with overall survival difference in hormone receptor-positive patients (P = 0.268). In multivariate Cox regression analysis, the test of interaction between surgery to chemotherapy interval and hormone receptor status was significant (P = 0.015). Moreover, when the multivariate analysis was restricted to hormone receptor-negative patients, longer surgery to chemotherapy interval was associated with worse overall survival among this subset of patients (P = 0.004). On the other hand, in multivariate analysis of factors affecting relapse-free survival, surgery to radiotherapy interval did not impact relapse-free survival (P = 0.439). Conclusion: Among hormone receptor-negative patients, delaying chemotherapy initiation beyond 6 weeks (after surgery) is associated with worse patient outcomes. Moreover, delaying radiotherapy initiation beyond surgery does not compromise outcomes in patients receiving long course adjuvant chemotherapy. (c) 2018 Elsevier Ltd. All rights reserved.