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
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Online Access:https://www.mdpi.com/2227-9059/13/6/1305
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author 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
author_facet 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
author_sort Gavin P. Dowling
collection DOAJ
description <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.
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spelling doaj-art-cdcbfcd569ce4257a8678c22f9dbfff52025-08-20T03:26:10ZengMDPI AGBiomedicines2227-90592025-05-01136130510.3390/biomedicines13061305Prognostic Significance of Delays in Initiation of Adjuvant Trastuzumab-Based Therapy in Patients with HER2-Positive Breast CancerGavin P. Dowling0Aisling Hegarty1Gordon R. Daly2Sandra Hembrecht3Cian M. Hehir4Gavin G. Calpin5Richard Hogan6David O’Reilly7Eithne Downey8Sinead Toomey9Liam Grogan10Oscar Breathnach11Michael Allen12Patrick G. Morris13Colm Power14Leonie S. Young15Arnold D. K. Hill16Bryan T. Hennessy17Department of Surgery, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandDepartment of Surgery, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandDepartment of Surgery, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandDepartment of Surgery, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandDepartment of Surgery, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandDepartment of Surgery, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandDepartment of Surgery, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandBeaumont RCSI Cancer Centre, Beaumont Hospital, D09 FT51 Dublin, IrelandBeaumont RCSI Cancer Centre, Beaumont Hospital, D09 FT51 Dublin, IrelandMedical Oncology Laboratory, Department of Molecular Medicine, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandBeaumont RCSI Cancer Centre, Beaumont Hospital, D09 FT51 Dublin, IrelandBeaumont RCSI Cancer Centre, Beaumont Hospital, D09 FT51 Dublin, IrelandDepartment of Surgery, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandBeaumont RCSI Cancer Centre, Beaumont Hospital, D09 FT51 Dublin, IrelandDepartment of Surgery, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandDepartment of Surgery, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandDepartment of Surgery, Royal College of Surgeons in Ireland, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, IrelandMedical Oncology Laboratory, Department of Molecular Medicine, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland<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.https://www.mdpi.com/2227-9059/13/6/1305breast cancertrastuzumabadjuvant therapytargeted therapybreast surgery
spellingShingle 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
Prognostic Significance of Delays in Initiation of Adjuvant Trastuzumab-Based Therapy in Patients with HER2-Positive Breast Cancer
Biomedicines
breast cancer
trastuzumab
adjuvant therapy
targeted therapy
breast surgery
title Prognostic Significance of Delays in Initiation of Adjuvant Trastuzumab-Based Therapy in Patients with HER2-Positive Breast Cancer
title_full Prognostic Significance of Delays in Initiation of Adjuvant Trastuzumab-Based Therapy in Patients with HER2-Positive Breast Cancer
title_fullStr Prognostic Significance of Delays in Initiation of Adjuvant Trastuzumab-Based Therapy in Patients with HER2-Positive Breast Cancer
title_full_unstemmed Prognostic Significance of Delays in Initiation of Adjuvant Trastuzumab-Based Therapy in Patients with HER2-Positive Breast Cancer
title_short Prognostic Significance of Delays in Initiation of Adjuvant Trastuzumab-Based Therapy in Patients with HER2-Positive Breast Cancer
title_sort prognostic significance of delays in initiation of adjuvant trastuzumab based therapy in patients with her2 positive breast cancer
topic breast cancer
trastuzumab
adjuvant therapy
targeted therapy
breast surgery
url https://www.mdpi.com/2227-9059/13/6/1305
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