Abstract SS1-11: Comprehensive analysis of health services, sociodemographic, clinical, and genomic factors driving locally advanced breast cancer mortality via a first-in-kind linkage of SEER-Medicare data with physical tumor samples
Authors: Robinson Timothy J , Wilson Lauren , Marcom Paul K , Troester Melissa , Lynch Charles F , Hernandez Brenda , Castellar Edgardo P , Brauer Heather Ann , Enewold Lindsey , Dinan Michaela 
Published: February 2021

Abstract
Background: There continues to be an active debate as to the relative contribution of health services, sociodemographic, clinical, and genomic factors in breast cancer disparities. Efforts to understand the contributions of each of these factors have historically focused on separate investigations of socioeconomic, demographic, and genomic elements. However, true multidisciplinary investigation of these factors requires the existence of datasets that combine each of these elements together into population-level, real world cohorts. To this end we created the first-in-kind linkage of SEER-Medicare data to physical tumor samples to combine clinical, health services, and genomic data into a single cohort and used it to investigate the impact of screening and socioeconomic status on early stage breast cancer biology and mortality.Methods: This retrospective study used formalin-fixed, paraffin-embedded (FFPE) breast cancer (BC) tissue collected between 1992-2006 within the Iowa and Hawaii SEER Residual Tissue Repositories (SEER-RTR). Medicare fee-for-service claims data were linked for participating patients age 65 and older. Molecular subtyping and exploratory genomic analyses were completed using the NanoString Breast Cancer 360 (BC360) gene expression panel containing the PAM50 classifier. Screening status was assessed by validated claims-based algorithms. Factors associated with overall (OS) & breast cancer-specific (BCS) survival were analyzed in women aged 66-75 with clinically high risk ER+ disease (M0, T1b+, LN+) using Cox proportional hazards models combining sociodemographic, clinical, and genomic data.Results: SEER-Medicare data were available for 1,232 women, of which 379 (30.7%) were diagnosed by screening mammogram. Screen-detected disease was associated with lower T stage, N stage, and improved OS (HR 0.72) & BCS (HR 0.68) in multivariable analysis. Molecular analysis of 130 luminal A/B cases revealed superior outcomes of luminal A and luminal B tumors compared to symptom detected tumors of the same molecular subtype (p = 0.02). In multivariable cox proportional hazards models increased overall mortality was associated with impoverished neighborhoods, PR- receptor status, upregulation of TGF-beta and p53 dysregulation, whereas protective factors included upregulation of androgen receptor (AR), stromal, and cytotoxicity signaling (all P&lt;0.05; Table 1). T2 vs. T1 tumor stage was associated with the largest observed differences in gene expression, and was associated with distinct changes in gene expression in luminal A vs. B disease including down regulation of interferon gamma signaling and MHCII expression in luminal B, but not luminal A, tumors.Conclusions and Relevance: Linkage of SEER, Medicare, and physical tumor specimen data is feasible and allows the combination of genomic analyses with clinical and health services data within population-level cohorts and may provide a novel means to elucidate links between biology, access, and disparities in breast cancer outcomes. Future research is warranted to conduct analogous prospective investigations of cancer disparities.
Table – Cox multivariable survival modelParameterAll-cause mortalityHR (95% CI)Symptomatic tumor1.59 (0.70 - 3.64)Stage N2+ vs N12.67 (0.48 -14.83)Stage T2 vs T13.49 (1.42 - 8.58)Aged 71-76 vs 66-702.30 (1.05 - 5.01)Comorbidity Score (ref=0)2+8.85 (1.88-41.73)High school dropout rate3.72 (1.36 -10.17)PR- vs PR+7.25 (1.96 -26.77)Luminal B vs Luminal A0.99 (0.40 - 2.49)AR signature0.21 (0.09 - 0.48)TGF beta signature6.97 (2.00 -24.33)Macrophages signature0.22 (0.08 - 0.60)BC cytotoxicity signature0.61 (0.43 - 0.88)p53 signature3.12 (1.51 - 6.47)
Citation Format: Timothy J Robinson, Lauren Wilson, Paul K Marcom, Melissa Troester, Charles F Lynch, Brenda Hernandez, Edgardo P Castellar, Heather Ann Brauer, Lindsey Enewold, Michaela Dinan. Comprehensive analysis of health services, sociodemographic, clinical, and genomic factors driving locally advanced breast cancer mortality via a first-in-kind linkage of SEER-Medicare data with physical tumor samples [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS1-11.