Timing of postmastectomy radiotherapy following adjuvant chemotherapy for high-risk breast cancer: A post hoc analysis of a randomised controlled clinical trial

Abstract

Purpose: To investigate the appropriate timing of radiotherapy (RT) after mastectomy and adjuvant chemotherapy for women with high-risk breast cancer.

Patients and methods: Post hoc analyses of 584 patients with stage II and III breast cancer from a randomised controlled clinical trial were performed. All patients underwent mastectomy followed by sequential chemotherapy and RT. The optimal cut-off values for the surgery-RT interval (SRI) and the chemotherapy-RT interval (CRI) for overall survival (OS) were determined using the hazard ratio for continuous predictors. The locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and OS rates were estimated using the Kaplan-Meier method. Multivariate analyses were performed using Cox proportional hazards regression.

Results: Median follow-up time was 83.5 months. Median SRI and CRI were 168 and 27 days, respectively. An SRI of >210 days was independently associated with higher DM (HR 2.65, 95% CI: 1.49-4.71; HR 2.78, 95% CI 1.51-5.26), lower OS (HR 2.44, 95% CI: 1.28-4.54; HR 2.50, 95% CI: 1.41-4.35), and lower DFS (HR 2.57, 95% CI: 1.45-4.57; HR 2.70, 95% CI: 1.45-5.00) than SRI of <180 or 180-210 days. Furthermore, a CRI of more than 42 days was independently associated with higher DM (HR 1.89, 95% CI: 1.17-3.06; HR 1.96, 95% CI: 1.19-3.22), lower OS (HR 2.44, 95% CI: 1.41-4.35; HR 1.92, 95% CI: 1.10-3.33), and lower DFS (HR 1.84, 95% CI: 1.14-2.96; HR 1.82, 95% CI: 1.12-2.94) than a CRI of <28 or 28-42 days. However, SRI and CRI had no significant effect on LRR.

Conclusions: Based on the present findings, the timing of the initiation of RT both after mastectomy and after the completion of adjuvant chemotherapy is crucial for patients with high-risk breast cancer.

Keywords: Breast neoplasm; Mastectomy; Prognosis; Radiotherapy; Timing.