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Meta-Analysis
. 2025 Aug:82:104516.
doi: 10.1016/j.breast.2025.104516. Epub 2025 Jun 9.

Prognostic significance of receptor conversion following neoadjuvant therapy in breast cancer: a systematic review & meta-analysis

Gavin P Dowling  1 , Gordon R Daly  2 , Cian M Hehir  2 , Maen M AlRawasdeh  3 , Gavin G Calpin  2 , Sami Almasri  3 , Sinead Toomey  4 , Leonie S Young  2 , Bryan T Hennessey  4 , Arnold D K Hill  2
Affiliations
Meta-Analysis

Prognostic significance of receptor conversion following neoadjuvant therapy in breast cancer: a systematic review & meta-analysis

Gavin P Dowling et al. Breast. 2025 Aug.

Abstract

Purpose: Receptor conversion following neoadjuvant therapy in breast cancer may influence prognosis and adjuvant treatment decisions. This systematic review and meta-analysis evaluated the prognostic significance of changes in hormone receptor (HR) and HER2 status after neoadjuvant therapy.

Methods: This study was performed in accordance with PRISMA guidelines. A systematic search of the literature was conducted to identify studies assessing the prognostic effect of receptor conversion after neoadjuvant treatment in breast cancer. Studies reporting receptor status before and after neoadjuvant therapy, with associated survival outcomes, were included. Pooled hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS) were calculated using random-effects models.

Results: Twenty-two studies (n = 5370) were included in this meta-analysis. HR gain demonstrated significantly improved DFS (HR 0.49, 95 % CI 0.25-0.97; p = 0.04), but no OS benefit. HR loss was associated with both significantly worse DFS (HR 3.42, 95 % CI 1.93-6.08; p < 0.001) and OS (HR 1.99, 95 % CI 1.04-3.84; p = 0.04). HER2 gain had a negative impact on DFS (HR 1.89, 95 % CI 1.00-3.58; p = 0.05), with no significant effect on OS. HER2 loss was associated with significantly poorer DFS (HR 1.92, 95 % CI 1.51-2.43; p < 0.001) and OS (HR 2.20, 95 % CI 1.44-3.38; p < 0.001).

Conclusion: This systematic review and meta-analysis demonstrates that receptor conversion following neoadjuvant therapy in breast cancer significantly impacts survival outcomes. Specifically, gaining HR positivity is associated with improved DFS, while losing HR positivity correlates with worse DFS and OS. With regards to HER2, gaining positivity is associated with worse DFS, and losing positivity is associated with worse DFS and OS, compared to patients who maintain their initial status. These findings underscore the potential importance of reassessing receptor status after neoadjuvant therapy to tailor subsequent treatment decisions accurately.

Keywords: Breast cancer; HER2; Hormone receptor; Neoadjuvant therapy; Prognosis; Receptor conversion; Targeted therapy.

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Conflict of interest statement

Declaration of competing interest The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Flow diagram.
Fig. 2
Fig. 2
Prognostic significance of HR gain after neoadjuvant therapy.
Fig. 3
Fig. 3
Prognostic significance of HR loss after neoadjuvant therapy.
Fig. 4
Fig. 4
Prognostic significance of HER2 Gain after neoadjuvant therapy.
Fig. 5
Fig. 5
Prognostic significance of HER2 Loss after neoadjuvant therapy.
See this image and copyright information in PMC

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