Molecular subtype and survival in inflammatory breast cancer: A contemporary population-based analysis.

e13088 Background: Inflammatory breast cancer (IBC) is a rare and highly aggressive form of breast cancer with persistently poor outcomes. Although prior population-based studies have demonstrated prognostic heterogeneity by hormone receptor and HER2 status, much of the existing evidence is derived from relatively small cohorts and earlier treatment eras. As treatment paradigms have evolved, updated analyses using large, contemporary population-based datasets are needed to better characterize survival patterns across receptor-defined subtypes. Methods: We conducted a retrospective population-based cohort study using Surveillance, Epidemiology, and End Results (SEER) data from 2000–2020, including patients diagnosed with inflammatory breast cancer. Patients were identified using SEER criteria and required to have known estrogen receptor (ER), progesterone receptor (PR), and HER2 status for molecular subtype classification. Tumors were categorized as HR+/HER2–, HR+/HER2+, HR–/HER2+, or triple-negative. Overall survival was defined as time from diagnosis to death from any cause or last follow-up. Survival was evaluated using Kaplan–Meier methods with log-rank testing and multivariable Cox proportional hazards models adjusted for demographic, socioeconomic, clinicopathologic, and treatment-related factors. Analyses were conducted using complete-case data. A study protocol was developed prior to analysis and reviewed by faculty collaborators. Results: The study cohort included 5,920 patients with inflammatory breast cancer. Overall survival differed significantly by molecular subtype (log-rank p < 0.0001). In multivariable analyses, triple-negative disease was associated with significantly worse overall survival compared with HR+/HER2– tumors (HR 1.65, 95% CI 1.54–1.77), whereas HR+/HER2+ tumors demonstrated improved survival (HR 0.66, 95% CI 0.54–0.80). In contrast, survival among patients with HR–/HER2+ tumors did not differ significantly from the reference group. Receipt of chemotherapy was independently associated with improved overall survival (HR 0.61, 95% CI 0.56–0.67). Conclusions: In this large contemporary population-based analysis, molecular subtype remained a major determinant of prognosis in inflammatory breast cancer. Triple-negative disease was associated with substantially poorer survival, while HER2-positive tumors, particularly those that were hormone receptor–positive, demonstrated more favorable outcomes. These findings confirm and extend prior population-based analyses by providing stable, modern-era estimates of subtype-specific survival in IBC, and may inform prognostic counseling and subtype-specific treatment considerations.