Abstract Background: Metastatic breast cancer involving the brain is associated with a poor prognosis and represents a clinically challenging subset of patients. Understanding how additional metastatic sites, such as the lungs, impact outcomes and whether demographic or socioeconomic disparities contribute to these patterns remains critical for improving care equity. This study, therefore, aims to investigate whether differences in metastatic patterns are linked to demographic or socioeconomic disparities, or are primarily driven by tumor biology. Methods: This retrospective cohort study utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify female patients diagnosed with breast cancer and brain metastases between 2000 and 2021. Patients were categorized into two groups: those with brain-only metastases and those with both brain and lung metastases. Key variables included age, race, breast cancer subtype, income, rural-urban residence, and marital status. Survival differences were assessed using Kaplan–Meier analysis with log-rank testing. Logistic regression was performed to identify predictors of concurrent brain and lung metastases. All statistical analyses were conducted using IBM SPSS Statistics 27. Results: In this cohort of 3,127 patients with breast-cancer brain metastases, 49.1 % (n = 1,535) presented with brain-only disease, whereas 50.9 % (n = 1,592) already harbored simultaneous lung lesions. Survival differed sharply between the two groups: median overall survival was 28.0 months (95 % CI 25.8–30.2) for brain-only disease versus 19.6 months (95 % CI 17.8–21.3) when lung metastases were also present, a highly significant nine-month gap confirmed by log-rank testing (χ2 = 41.782, p 0.001). This pattern did not show statistically significant associations with traditional sociodemographic factors such as race, income, rurality, or marital status. Breast cancer subtype emerged as the sole independent predictor of concurrent brain and lung metastases both in univariable analysis (p = 0.003) and multivariable modeling (p = 0.034). Conclusion: Our findings reinforce that metastatic distribution, particularly when influenced by breast cancer subtype, remains a critical determinant of survival disparities within the already vulnerable population of patients with brain-involved metastatic breast cancer. The consistent presence of lung metastases across racial and socioeconomic groups suggests that biology, not access to care, mainly drives this deadly spread. Still, the 9-month survival disadvantage for patients with both brain and lung disease affects all groups equally. These data call for equity-focused, subtype-stratified surveillance protocols and therapeutic strategies that can intercept or more aggressively treat thoracic progression. By identifying where disparities do and do not exist, our findings guide efforts to allocate resources, tailor trials, and develop interventions that reduce outcome gaps and address biological drivers of metastatic inequity. Citation Format: Mohammad-Amer A. Tamimi, Yousef A. Ateiwi, Fares A. Qtaishat, Abdullah Abulraheem, Ahmad Alkayyat, Jana Tarawneh, Layan AlDaher, Sarah Abdallah, Adham Musa, Sara Qutaishat. Metastatic patterns and survival in breast cancer with brain involvement: Are disparities or biology to blame? abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C007.
Tamimi et al. (Thu,) studied this question.