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

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

<b>Purpose:</b> 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-positi...

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Main Authors: Gavin P. Dowling, Aisling Hegarty, Gordon R. Daly, Sandra Hembrecht, Cian M. Hehir, Gavin G. Calpin, Richard Hogan, David O’Reilly, Eithne Downey, Sinead Toomey, Liam Grogan, Oscar Breathnach, Michael Allen, Patrick G. Morris, Colm Power, Leonie S. Young, Arnold D. K. Hill, Bryan T. Hennessy
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Biomedicines
Subjects:
breast cancer
trastuzumab
adjuvant therapy
targeted therapy
breast surgery
Online Access:https://www.mdpi.com/2227-9059/13/6/1305
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Summary:<b>Purpose:</b> 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. <b>Methods:</b> 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. <b>Results:</b> Patients with TTAT greater than 42 days had significantly worse OS, DFS, and DMFS (<i>p</i> = 0.036, <i>p</i> = 0.045, and <i>p</i> = 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; <i>p</i> = 0.027) and OS (HR 4.48; <i>p</i> = 0.004). These findings indicate that even moderate delays in trastuzumab initiation can adversely affect survival. <b>Conclusions:</b> 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.
ISSN:2227-9059

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