RMTD-04 the Incidence of Brain Metastases (Brm) as a First Site of Metastatic Recurrence Among Patients With Early-Stage Breast Cancer (Bc): A Systematic Review and Meta-Analysis

BACKGROUND In the pivotal KEYNOTE-522 and KATHERINE trials for patients with early-stage triple-negative (TN) and human epidermal growth factor receptor-2 (HER2)+ BC, the incidence of BrM as a first site of metastatic recurrence ranged from 2.6% to 5.1%. However, the incidence of BrM as a first site of metastatic recurrence has not been systematically evaluated. METHODS A literature search was conducted using the MedLine, Embase and Cochrane Library databases from January 2000 to July 2024 using terms related to BC, BrM, and incidence. References of included studies and trials from the Early Breast Cancer Clinical Trialists’ Collaborative Group meta-analysis were also reviewed. The reported incidence of BrM and follow-up duration were extracted by BC subtype; random effects models were used to calculate pooled overall estimates for BrM incidence. RESULTS 3863 articles were compiled from which 36 studies met inclusion criteria; data from 24 retrospective studies, 4 prospective studies and 12 randomized trials were included for analysis. The incidence of BrM as a first site of metastatic relapse among patients with HER2+, TN, and hormone receptor (HR)+/HER2− BC was reported in 21, 11 and 6 studies, respectively. The pooled cumulative incidence of BrM was 3.1% for the TN (median follow-up, 55 months; range, 18.0–156.0 months), 2.4% for the HER2+ (median follow-up, 49 months; range, 26.9–93.0 months), and 0.70% for the HR+/HER2− subgroup (median follow-up, 72.7 months; range, 49.0–93.0 months). The corresponding incidences per 100 patient-years were 0.83 (95% CI: 0.54–1.11) for the TN, 0.48 (95% CI: 0.36–0.60) for the HER2+, and 0.04 (95% CI: 0.00–0.14) for the HR+/HER2− subgroup. CONCLUSION Given a low risk of BrM among patients with early-stage BC, efforts to identify clinical, pathological and genomic features associated with BrM development are warranted to identify “enrichment” cohorts for future BrM prevention trials.