Abstract Background: Symptomatic medullary infiltration (SMI) in metastatic breast cancer is rare and associated with significant hematologic compromise. No standard treatment exists, and data-guided management are limited. Retrospective studies suggest similar overall survival (OS)with chemotherapy (CT) and endocrine therapy combining aromatase inhibitors (AI) andCDK4/6 inhibitors. However, direct comparisons between CT and AI alone are scarce. This study evaluated OS in patients with SMI treated with CT or AI-based endocrine therapy in the first- or second-line setting. Methods: We retrospectively reviewed records of patients with metastatic breast cancer who underwent bone marrow biopsy at a single academic center from 2015 to 2023. Inclusion criteria were histologically confirmed SMI, symptomatic cytopenias, and receipt of either CT or hormone therapy (HT; AI or tamoxifen ± ovarian suppression, excluding CDK4/6 inhibitors) in the first or second line. Clinical, pathological, and survival data were analyzed. OS was estimated using Kaplan-Meier methods; independent prognostic factors were assessed via multivariable Cox regression. Results: Of 306 patients screened, 24 met inclusion criteria. Median age was 53 years; all tumors were hormone receptor-positive, and 5 were HER2-positive. Common manifestations included anemia (96%), thrombocytopenia (62%), dacrocytosis (58%), and leukopenia (33%). Most patients (n=23) had ≥3 metastatic sites; ECOG performance status was 0 (n=1), 1 (n=10), 2 (n=10), and 3 (n=3). In the first-line setting, median OS was 5.0 months with CT versus 2.0 months with HT (HR 2.4; 95% CI 0.9-6.4; p = 0.07). On multivariable analysis, CT was associated with improved OS (HR 0.06; p = 0.01), while HER2-positivity (HR 50; p = 0.01) and ≥3 metastatic sites (HR 4.3; p = 0.004) were associated with worse outcomes. Latin ethnicity emerged as a protective factor (HR 0.01; p = 0.01). In the second-line setting, CT conferred longer OS (5.0 vs.1.4 months; HR 0.2; p = 0.02), although not confirmed in the multivariable model. Age (HR 1.2;p = 0.02), ECOG 3 (HR 369; p = 0.04), and non-Latin race (HR 0.01; p = 0.03) were significant predictors of poorer survival. Conclusions: In this real-world cohort of patients with SMI from metastatic breast cancer, chemotherapy was associated with improved OS in the first-line setting compared to hormone therapy. No survival benefit was observed in second-line. HER2-positivity, advanced age, poor performance status, and extensive metastatic disease were associated with worse outcomes. Latin ethnicity was consistently protective across treatment lines. Citation Format: R. R. Miranda, L. d. Graziano, G. C. Trofa, W. A. De Lima, L. Testa. Survival Outcomes of Chemotherapy Versus Endocrine Therapy in Symptomatic Medullary Infiltration from Metastatic Breast Cancer: A Retrospective Real-World Study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-05-03.
Miranda et al. (Tue,) studied this question.