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

Abstract

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.

Keywords: Breast cancer; Chemotherapy; Radiotherapy; Timelines.