Prognostic Significance of Delays in Initiation of Adjuvant Trastuzumab-Based Therapy in Patients with HER2-Positive Breast Cancer

Abstract

Purpose: Adjuvant trastuzumab therapy has improved outcomes in HER2-positive breast cancer, but the impact of the timing of its initiation remains unclear. This study evaluates the effect of time to adjuvant trastuzumab-based therapy (TTAT) after surgery on survival in HER2-positive breast cancer. Methods: In this retrospective study, HER2-positive breast cancer patients treated with surgery followed by adjuvant trastuzumab without prior neoadjuvant therapy were analyzed. Patients were grouped by TTAT ≤ 42 days or >42 days post-surgery. Key endpoints included overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS), evaluated through Kaplan-Meier and Cox regression analyses. Results: Patients with TTAT greater than 42 days had significantly worse OS, DFS, and DMFS (p = 0.036, p = 0.045, and p = 0.048, respectively, log-rank test) than those initiating trastuzumab within 42 days. On multivariate analysis, delays beyond 42 days were associated with a significantly increased risk of recurrence and mortality, showing reduced DFS (HR 2.52; p = 0.027) and OS (HR 4.48; p = 0.004). These findings indicate that even moderate delays in trastuzumab initiation can adversely affect survival. Conclusions: Delaying trastuzumab initiation beyond 42 days post-surgery negatively impacts survival in HER2-positive breast cancer, emphasizing the need for timely treatment. These results support clinical guidelines advocating prompt initiation of adjuvant therapy to improve long-term outcomes for HER2-positive patients.

Keywords: adjuvant therapy; breast cancer; breast surgery; targeted therapy; trastuzumab.

Figure 1

Flowchart outlining the selection of patients from the Breast Cancer Surgical Database for inclusion in the study of HER2-positive non-metastatic breast cancer treated with adjuvant trastuzumab. From an initial cohort of 3135 patients in the database, 397 patients with HER2-positive non-metastatic breast cancer who received trastuzumab therapy were identified. Of these, 130 patients who received neoadjuvant trastuzumab were excluded, resulting in 267 patients who received adjuvant trastuzumab. An additional 40 patients were excluded due to insufficient data regarding the start date of trastuzumab therapy. The final study population included 227 patients with HER2-positive non-metastatic breast cancer treated with adjuvant trastuzumab and complete treatment data.

Figure 2

Overall survival (OS) of patients with TTAT ≤ 42 days (n = 80) compared to those with TTAT > 42 days (n = 147).

Figure 3

Disease-free survival (DFS) of patients with TTAT ≤ 42 days (n = 80) compared to those with TTAT > 42 days (n = 147).

Figure 4

Distant Metastasis-Free Survival (DMFS) of patients with TTAT ≤ 42 days (n = 80) compared to those with TTAT > 42 days (n = 147).