J Neurooncol. 2026 Jul 24;179(1):14. doi: 10.1007/s11060-026-05711-3.
ABSTRACT
BACKGROUND: Brain metastases (BrM) are a major cause of morbidity among patients with breast cancer (BC), particularly those with HER2+ or triple-negative disease. The relationship between neoadjuvant chemotherapy (NAC) and subsequent risk of BrM in patients with early-stage BC remains poorly defined.
METHODS: We conducted a single-centre retrospective cohort study of 457 consecutive patients who were treated with NAC for early-stage BC at Sunnybrook Odette Cancer Centre between 2008 to 2019, among whom 25 developed BrM (cohort 1). To evaluate factors associated with shorter time to BrM development, an additional 129 patients with BC who received NAC and were subsequently diagnosed with BrM were identified (cohort 2). Descriptive statistics were used to summarize patient and treatment characteristics. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and identify factors associated with the development of BrM. Univariable analyses (UVA) were performed for all covariates. Bayesian Information Criteria determined best models from subsets of covariates when performing multivariable analyses (MVA).
RESULTS: Among 586 patients, the median age at BC diagnosis was 49.0 (IQR: 42-58) years. The most common BC subtype was HER2+ (n = 225, 38.4%), followed by hormone receptor (HR)+/HER2- (n = 213, 36.3%) and triple negative BC (n = 132, 22.5%). Following NAC, 134 patients (22.9%) had a pathologic complete response (pCR) and 409 (69.8%) had residual disease. In the overall cohort, the median time from BC diagnosis to BrM development was 38.0 (IQR 19.1-70.9) months. In cohort 1, 25 patients (5.5%) developed BrM with a median follow-up of 43.1 months. Median time to BrM was shortest for patients with triple-negative BC (18.0 months), followed by those with HER2+ (32.0 months), and HR+/HER2- disease (49.1 months). In the pooled cohort (n=586), multivariable analysis identified residual nodal involvement (HR 4.46 [95% CI 2.67-7.45], p<0.0001), inflammatory BC (HR 3.11 [95% CI 1.95-4.96], p<0.0001), and HER2+ or triple-negative subtype (HR 2.87 [95% CI 1.80-4.58], p<0.0001) as independently associated with shorter time to BrM development.
CONCLUSIONS: Among patients treated with NAC for early-stage BC, residual nodal disease, inflammatory BC, and HER2+ or triple-negative subtype are associated with a higher risk of BrM development. Whether BrM screening is warranted among patients with these high-risk features warrants evaluation.
CLINICAL TRIAL NUMBER: Not applicable.
PMID:42496928 | DOI:10.1007/s11060-026-05711-3
