RMTC-08 POPULATION-LEVEL SURVIVAL IMPROVEMENT IN HR+/HER2+ DE NOVO BREAST CANCER WITH BRAIN METASTASES IN THE ADC ERA: A SEER ANALYSIS

Abstract

Antibody-drug conjugates (ADCs) including trastuzumab deruxtecan have demonstrated efficacy in HER2+ breast cancer brain metastases (BCBM) in clinical trials, yet population-level evidence of survival improvement and equitable distribution remains limited. Using SEER Research Plus data (17 registries, Nov 2024), we identified female patients with de novo invasive breast cancer and synchronous brain metastases at diagnosis (2010–2022; N = 2,899; N = 2,432 with known molecular subtype). Patients were stratified by subtype and era (pre-ADC: 2010–2019; ADC era: 2020–2022). Cause-specific survival (CSS) was estimated by Kaplan-Meier method with log-rank testing. Multivariable Cox regression adjusted for age, race, census tract income quintile, marital status, and extracranial metastatic burden. Racial disparity analyses were restricted to the HR+/HER2+ subgroup, the only subtype with significant ADC-era survival improvement. As SEER lacks treatment data, ADC attribution is inferential and based on temporal and subtype-specific patterns. Among 472 HR+/HER2+ patients, median CSS improved from 19 months (2010–2019) to not reached (2020–2022; log-rank p = 0.046). Twelve-month CSS increased from 59% to 69% and 24-month CSS from 46% to 56%. HR+/HER2- (p = 0.095) and TNBC (p = 0.113) showed no significant improvement. HR-/HER2+ patients (n = 331) showed no improvement (15 vs 13 months, p = 0.857). Era-by-subtype interaction was not significant (p = 0.76), likely due to limited power. Diagnosis in 2020–2022 remained independently associated with improved CSS (HR 0.79, 95% CI 0.64–0.97, p = 0.025). In HR+/HER2+ analyses Non-Hispanic White patients had a 45% hazard reduction in the ADC era (HR 0.548, 95% CI 0.304–0.989, p = 0.046), while Non-Hispanic Black patients showed a non-significant trend (n = 28, 10 events; HR 0.404, 95% CI 0.105–1.55, p = 0.187). Income adjustment reduced excess hazard. No racial survival differences were observed within income strata. This population-level study suggests improved survival in HR+/HER2+ BCBM in the ADC era. Findings suggest socioeconomic disparities in benefit, warranting investigation with future SEER data.