Impact of High Lymph Node Burden on Brain Metastases in Patients Who Achieved Pathological Complete Response after Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.

Purpose: This study aims to investigate the clinical characteristics, outcomes, and predictors of brain metastases in 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 OS (p<0.001). Median DMFS 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) stage were the strongest predictors of brain metastases (SCN FNA: OR=12.9, p<0.001; cN3: OR=12.1, p<0.001). Multivariable Cox regression analysis revealed that positive SCN FNA and cN3 stage were strong predictors of reduced DMFS (SCN FNA: HR=2.5, 95% CI: 1.3-3.6, p < 0.001; cN3: HR=11.3, 95% CI: 4.9-33.0, 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.