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. 2025 Sep;32(5):1035-1043.
doi: 10.1007/s12282-025-01731-5. Epub 2025 Jun 8.

Stereotactic radiosurgery for HER2-positive breast cancer brain metastases: prognostic factors and the evolving role of anti-HER2 therapies

Menekse Turna  1 , Berna Akkus Yıldırım  2 , Çakır Numanoglu  2 , Muhammed Emin Gül  2 , Mustafa Halil Akboru  2 , Rashad Rzazade  3 , Mehmet Doğu Canoğlu  3 , Hale Başak Çağlar  3
Affiliations

Stereotactic radiosurgery for HER2-positive breast cancer brain metastases: prognostic factors and the evolving role of anti-HER2 therapies

Menekse Turna et al. Breast Cancer. 2025 Sep.

Abstract

Purpose: This study aims to evaluate the clinical outcomes of SRS in patients with HER2-positive breast cancer brain metastases, focusing on survival, local control, and the influence of systemic therapies and clinical factors.

Methods: A retrospective analysis was conducted on 60 patients with HER2-positive breast cancer and brain metastases treated with SRS. Patient demographics, tumor characteristics, treatment parameters, and follow-up data were collected.

Results: The median follow-up was 21 months. 1-year, 2-year, and 3-year survival rates of 96%, 73%, and 50%, respectively. Factors associated with shorter OS included the presence of neurological deficits (p = 0.003), tumor diameter > 2.5 cm (p = 0.016), more than three brain metastases (p = 0.046), cumulative GTV volume greater than 2.63 cm3 (p = < 0.001), and the development of brain metastases within 3 years of the primary cancer diagnosis (p = 0.022). Local control rates were 98% at 1 year and 80% at 2 years. Distant brain metastasis-free survival rates were 91% at 1 year and 63% at 2 years. Patients receiving more than one line of anti-HER2 therapy before SRS showed significantly improved OS (p = 0.007) but had a higher incidence of leptomeningeal disease (p = 0.048). Radiation necrosis occurred in 8.3% of patients, predominantly after prolonged follow-up.

Conclusion: SRS combined with modern systemic therapies achieves favorable outcomes in HER2-positive breast cancer brain metastases, with improved survival and high local control rates. These findings highlight the need for personalized treatment strategies integrating local and systemic therapies to optimize intracranial disease management in this patient population.

Keywords: Anti-HER2 therapies; Brain metastases; HER2-positive breast cancer; Leptomeningeal disease; Stereotactic radiosurgery.

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Conflict of interest statement

Declarations. Conflict of interest: None.

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