Abstract PS2-10-11: Evaluating the impact of neighborhood deprivation on CDK4/6 inhibitor use, outcomes, and circulating tumor DNA (ctDNA) alterations in patients with metastatic breast cancer

Abstract Background: We previously showed lower rates of PI3K-targeted treatment use and shorter overall survival in patients with metastatic breast cancer (MBC) living in disadvantaged neighborhoods (Podany et al., ASCO 2025) using the validated Neighborhood Atlas Area Deprivation Index (ADI, Kind et al., NEJM 2018). ADI includes 17 measures of neighborhood disadvantage, including poverty, employment, and education. We sought to determine the use of CDK4/6 inhibitors (CDK4/6i), prognostic associations in patients on CDK4/6i with ctDNA somatic profiles, and outcomes of patients with or without CDK4/6i by ADI. Methods: This retrospective, multi-institution cohort study included 1127 patients with MBC and ctDNA testing with the Guardant360 assay treated at Washington University in St. Louis (N = 634), Massachusetts General Hospital (N = 313), Northwestern University (N = 71), and Weill Cornell (N = 109). Patient-reported 9-digit zip codes were converted into national ADI ranks (0-100) and divided into high deprivation (HDep, rank ≥60) and low deprivation (LDep, rank 60) based on prior studies. Patients were evaluated for use of CDK4/6i in the first and second line setting by ADI. Progression-free survival (PFS) was evaluated in the first line by CDK4/6i use and ADI. Multivariate models were then designed to determine prognostic differences in somatic mutations by ADI. Results: 335 patients (29.7%) lived in HDep neighborhoods, including 59 of the 203 patients (29.0%) with hormone receptor-positive (HR+) HER2 negative (HER2-) MBC and evaluable zip codes and first line treatment information. 144 of these HR+ HER2- patients received CDK4/6i in the first line and 40 received CDK4/6i in the second line. There was no significant difference in CDK4/6i use in the first line by ADI (74.3% in LDep vs 62.7% in HDep, p = 0.099) or second line (29.1% vs 28.6%, p = 0.96). Patients living in LDep neighborhoods were more likely to experience disease progression on CDK4/6i if they had a baseline ESR1 single nucleotide variation (snv) on ctDNA profiling (Hazard ratio HR 2.22, 95% confidence interval CI 1.08-4.54, p = 0.03) despite equal incidence (7.5% in LDep, 8.1% in HDep). Patients living in HDep neighborhoods were more likely to have progression on CDK4/6i if they had an ERBB2 snv on ctDNA profiling (HR 8.20, 95% CI 1.57 - 42.93, p = 0.013). There was no statistically significant difference in PFS between patients in LDep and HDep neighborhoods on CDK4/6i (12.0 vs 15.9 months, p = 0.5). Discussion: Patients with MBC living in more impoverished, HDep neighborhoods were equally likely to receive CDK4/6i and had similar PFS to patients on therapy compared to patients living in LDep neighborhoods. These data are reassuring that patients with MBC were equally likely to receive standard-of-care therapy with CDK4/6i therapy regardless of neighborhood deprivation. This finding differs from our previous work, which identified disparities in PI3K inhibitor use, and suggests more equitable use of a therapy that does not require identification of a molecular target. Patients in LDep neighborhoods were more likely to have disease progression on CDK4/6i if they had an ESR1 mutation. This finding is of potential clinical interest and will be the focus of future research, including assessing choice of endocrine therapy and CDK4/6i by ADI. Citation Format: E. L. Podany, S. Tapiavala, L. Foffano, A. Medford, N. Heater, C. Reduzzi, E. Nicolo, L. Pontolillo, A. Putur, D. Jaber, K. K. Clifton, M. Lipsyc-Sharf, F. Ademuyiwa, F. Puglisi, W. Gradishar, C. X. Ma, L. Gerratana, A. Bardia, M. Cristofanilli, A. A. Davis. Evaluating the impact of neighborhood deprivation on CDK4/6 inhibitor use, outcomes, and circulating tumor DNA (ctDNA) alterations in patients with metastatic breast cancer 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 PS2-10-11.