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Original Article
- Breast cancer
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Impact of High Lymph Node Burden on Brain Metastases in Patients Who Achieved Pathological Complete Response after Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer
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Seung Ah Lee, Ki Jo Kim, Do Youn Woen, Su Min Lee, Kawon Oh, Cho Eun Lee, Woong Ki Park, Ji Won Yoo, Dong Seung Shin, Jai Min Ryu, Se Kyung Lee, Byung Joo Chae, Jonghan Yu, Seok Won Kim, Seok Jin Nam, Ji-Yeon Kim, Yeon Hee Park, Eun Young Ko, Eun Sook Ko, Jeong Eon Lee
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Cancer Res Treat. 2026;58(3):780-789. Published online July 8, 2025
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DOI: https://doi.org/10.4143/crt.2025.219
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Abstract
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Supplementary Material
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- Purpose
This study aims to investigate the clinical characteristics, outcomes, and predictors of brain metastases in human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer patients who achieved pathological complete response (pCR) following neoadjuvant chemotherapy (NAC). This research seeks to inform surveillance strategies and optimize management for high-risk subgroups.
Materials and Methods
A retrospective analysis of 1,757 patients (2008-2022) classified them into pCR (n=914) and non-pCR (n=843) groups post-NAC. Collected data included demographics, clinical features, and metastasis parameters. Survival outcomes and brain metastasis predictors were assessed using Kaplan-Meier curves, Cox models, and logistic regression.
Results
Among pCR patients, brain metastases accounted for 54.2% of distant metastases, significantly affecting overall survival (p < 0.001). Median distant metastasis-free survival was shorter for brain metastases (13.4 months) compared to extracranial metastases (31.1 months) in the pCR group (p=0.005). Positive supraclavicular node (SCN) fine needle aspiration (FNA) and clinical N3 (cN3) category were the strongest predictors of brain metastases (SCN FNA: odds ratio [OR], 12.9; p < 0.001; cN3: OR, 12.1; p < 0.001). Multivariable Cox regression analysis revealed that positive SCN FNA and cN3 category were strong predictors of reduced distant metastasis-free survival (SCN FNA: hazard ratio, 2.5; 95% confidence interval [CI], 1.3 to 3.6; p < 0.001; cN3: hazard ratio, 11.3; 95% CI, 4.9 to 33.0; p < 0.001).
Conclusion
This study highlights the challenges of brain metastases in HER2-positive pCR patients, emphasizing the need for tailored therapeutic strategies and enhanced surveillance. High lymph node burden prior to NAC is a significant factor in risk assessment. Therefore, it may be advisable to recommend post-surgery surveillance for high-risk patients.
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