Differences in genomic profiles, targeted treatment use, and overall survival in patients with metastatic breast cancer by Area Deprivation Index.

Abstract

1046 Background: We previously showed racial differences in circulating tumor DNA (ctDNA) profiles and PI3K inhibitor (PI3Ki) use in patients (pts) with metastatic breast cancer (mBC); however, these findings may be influenced by socioeconomic disadvantage. A validated measure to explore this is the Neighborhood Atlas Area Deprivation Index (ADI, Kind et al NEJM 2018), which includes 17 measures of neighborhood disadvantage such as poverty, employment, and education. We sought to determine differences in genomic profiles, PI3Ki use, and overall survival (OS) in pts with mBC by ADI. Methods: This retrospective cohort study analyzed 1127 pts with mBC and ctDNA testing using the Guardant360 assay who were treated at Washington University in St. Louis (N = 634), Massachusetts General Hospital (N = 313), Weill Cornell (N = 109), and Northwestern University (N = 71). 9-digit zip codes were converted into national ADI ranks (0-100) divided into high deprivation (HDep, rank ≥60) and low deprivation (LDep, rank < 60) groups based on prior studies. Multivariate models were designed to determine genomic and prognostic differences by ADI. Pts with PIK3CA mutations were evaluated by ADI and use of PI3Ki in the second line or beyond, either through clinical trial enrollment or after FDA approval. OS from time of first ctDNA test was stratified by ADI and self-reported race. Results: The cohort included 165 Black pts (14.6%) and 335 pts (29.7%) from HDep zip codes. Black pts were more likely to be from HDep areas (Odds ratio [OR] 3.82, 95% confidence interval [CI] 2.62-5.57, P < 0.001). There were no differences in mBC subtype between ADI groups. Pts with HR+ HER2- mBC in the HDep group were significantly less likely to receive PI3Ki vs LDep (8/46, 17.4% vs 33/90, 36.7%, P = 0.02) despite equal incidence of PIK3CA mutations. Pts in the HDep group were more likely to have TP53 single nucleotide variants (snv) (OR 1.58, 95% CI 1.18-2.10, P = 0.002) and less likely to have AKT1 snv (OR 0.29, 95% CI 0.11-0.80, P = 0.017). Among pts in the HDep group, worse prognosis was seen in pts who self-identified as Black (hazard ratio [HR]1.51, 95% CI 1.02-2.25, P = 0.04), had PIK3CA snv (HR 1.73, 95% CI 1.23-2.44, P = 0.002), or TP53 snv (HR 1.56, 95% CI 1.12-2.17, P = 0.009). Median OS was significantly shorter in the HDep vs LDep group (24 months [mos] vs 28 mos, P = 0.04) and significantly lower for Black pts in the HDep vs Black pts with LDep or White pts with HDep or LDep (15 mos vs 25-28 mos, P = 0.02). Conclusions: In this multi-institutional cohort, we identified significant disparities in the use of PI3Ki in HDep neighborhoods and higher rates of TP53 snv, which are associated with aggressive tumor biology. Pts with mBC in HDep areas, especially Black pts, had shorter OS. Further research is needed to validate these findings, determine the root causes of these disparities, and implement change to achieve equity in precision medicine use.