Brain Radiotherapy Combined with Targeted Therapy for HER2-Positive Breast Cancer Patients with Brain Metastases

Abstract

Background: Research on the sequencing of brain radiotherapy and targeted chemotherapy after brain metastasis (BM) in HER2-positive breast cancer patients is limited and inconclusive. This study investigated the efficacy of sequential delivery of radiotherapy and targeted therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with BM.

Methods: Fifty-seven patients were categorized into two groups: the targeted-radiotherapy group (receiving 2-8 cycles of anti-HER2-targeted therapy followed by radiotherapy after BM) and the radiotherapy-targeted group (undergoing radiotherapy first, followed by regular anti-HER2-targeted therapy). The study endpoints were intracranial progression-free survival (iPFS) and overall survival. Factors associated with intracranial progression and mortality were assessed by univariate and multivariate Cox proportional hazards analysis.

Results: Patients in the radiotherapy-targeted group had better iPFS (P < 0.001), while there was no significant difference in overall survival between the two groups (P = 0.145). Multivariate Cox analysis showed that different sequential treatment groups were independent prognostic factors for iPFS. In patients with a modified breast graded prognostic assessment score of 3.5-4.0, the median survival time was 26 months in the radiotherapy-targeted group and 22 months in the targeted-radiotherapy group (P = 0.019).

Conclusion: Overall, radiotherapy followed by targeted therapy may improve survival in HER2-positive breast cancer patients with BM, particularly in those with a modified breast graded prognostic assessment score of 3.5-4.0.

Keywords: HER2; HER2-targeted drugs; brain metastasis; breast cancer; craniocerebral radiotherapy.

Figure 1

Flow chart of patients included in the study.

Figure 2

Magnetic Resonance Imaging (MRI) for breast cancer combined with brain metastasis in a 45-year-old female patient. T1WI revealed an irregular hypointense nodule in the right precentral gyrus; T2WI showed a slightly hyperintense signal; T2Flair demonstrated a hyperintense signal; and T1-CE displayed significant enhancement of the lesion.

Figure 3

Magnetic Resonance Imaging (MRI) for breast cancer combined with brain metastasis in a 50-year-old female patient. T1WI revealed an irregular hypointense nodule in the cerebellar vermis; T2WI and T2Flair showed slightly hyperintense signals; diffusion-weighted imaging (DWI) presented an isointense signal; the mean apparent diffusion coefficient (ADC) value of the lesions was 0.813 x 10(-3) mm²/s; and T1-CE demonstrated significant enhancement of the lesion.

Figure 4

Kaplan-Meier analysis comparing intracranial progression-free survival (a) and overall survival (b) in the radiotherapy-targeted group and the targeted-radiotherapy group.

Figure 5

Kaplan-Meier overall survival curves for modified breast graded prognostic assessment 2.0–3.0 group (a) and 3.5–4.0 group (b) in the radiotherapy-group and the targeted-radiotherapy group.

Figure 6

Kaplan-Meier overall survival curves for modified breast graded prognostic assessment scores in the radiotherapy-targeted group and the targeted-radiotherapy group.