Survival outcomes among patients with breast cancer and leptomeningeal disease.

Despite advances in metastatic breast cancer (MBC) management, leptomeningeal disease (LMD) prognosis remains poor. This study evaluates clinicopathological and treatment factors influencing outcomes of MBC patients with LMD treated with radiotherapy (RT). We conducted a retrospective analysis of patients with MBC treated with RT for brain metastases (BrM) between 2005 and 2019. LMD diagnosis was made via magnetic resonance imaging (MRI). Multivariable analysis (MVA) identified variables associated with brain-specific progression-free survival (bsPFS) and overall survival (OS). Among 691 MBC patients treated with RT for BrM, 161 (23%) had LMD, either at initial presentation (50/161) or after BrM treatment. Patients with LMD were younger, more likely to have ER + disease, more likely to have undergone surgery for BrM, and less likely to have received prior whole-brain RT. HER2+ LMD was associated with longer bsPFS (HR 0.47, 95% CI: 0.25-0.86, p = 0.01) and OS (HR 0.38, 95% CI: 0.2-0.75, p = 0.002). Median OS for triple-negative breast cancer was 3.7 months, 5.1 months for HR+/HER2 - and 15.4 months for HER2 + MBC. HER2-targeted therapy, either at or after LMD diagnosis, improved long-term survival (> 2 years) (Fisher's test, p < 0.05). Low Karnofsky Performance Status (KPS < 60) was linked to shorter bsPFS (HR 2.91, 95% CI: 1.49-5.69, p < 0.01) and OS (HR 3.37, 95% CI: 1.78-6.41, p < 0.001). These findings highlight the need for effective CNS-penetrating systemic therapies for HER2-negative breast cancer.