Abstract
Understanding interactions among health service, sociodemographic, clinical, and genomic factors in breast cancer disparities research has been limited by a disconnect between health services and basic biological approaches. To describe the first linkage of Surveillance, Epidemiology, and End Results (SEER)-Medicare data to physical tumor samples and to investigate the interaction among screening detection, socioeconomic status, tumor stage, tumor biology, and breast cancer outcomes within a single context. This population-based cohort study used tumor specimen blocks from a subset of women aged 66 to 75 years with newly diagnosed nonmetastatic, estrogen receptor-positive invasive breast cancer from January 1, 1993, to December 31, 2007. Specimens were obtained from the Iowa and Hawaii SEER Residual Tissue Repositories (RTRs) and linked with Medicare claims data and survival assessed through December 31, 2015. Data were analyzed from August 1, 2018, to July 25, 2021. Screening- vs symptom-based detection of tumors was assessed using validated claims-based algorithms. Demographic factors and zip code-based educational attainment and poverty socioeconomic characteristics were obtained via SEER. Molecular subtyping and exploratory genomic analyses were completed using the NanoString Breast Cancer 360 gene expression panel containing the 50-gene signature classifier. Factors associated with overall and breast cancer-specific (BCS) survival were analyzed using Cox proportional hazards regression models combining sociodemographic, clinical, and genomic data. SEER-Medicare data were available for 3522 women (mean [SD] age, 70.9 [2.6] years; 3049 [86.6%] White), of whom 1555 (44.2%) were diagnosed by screening mammogram. In the SEER-Medicare cohort, factors associated with increased BCS mortality included symptomatic detection (hazard ratio [HR], 1.49 [95% CI, 1.16-1.91]), advanced disease stage (HR for stage III, 2.33 [95% CI, 1.41-3.85]), and high-grade disease (HR, 1.85 [95% CI, 1.46-2.34]). The molecular cohort of 130 cases with luminal A/B cancer further revealed increased all-cause mortality associated with genomic upregulation of transforming growth factor β activation and p53 dysregulation (eg, p53 dysregulation: HR, 2.15 [95% CI, 1.20-3.86]) and decreased mortality associated with androgen receptor, macrophage, cytotoxicity, and Treg signaling (eg, androgen receptor signaling: HR, 0.23 [95% CI, 0.12-0.45]). Symptomatic detection (HR, 2.49 [95% CI, 1.19-5.20]) and zip codes with low levels of educational attainment (HR, 5.17 [95% CI, 2.12-12.60]) remained associated with mortality after adjusting for all clinical and demographic factors. Linkage of SEER-Medicare data to physical tumor specimens may elucidate associations among biology, health care access, and disparities in breast cancer outcomes. The findings of this study suggest that screening detection and socioeconomic status are associated with survival in patients with locally advanced, estrogen receptor-positive tumors, even after incorporating clinical and genomic factors.
Highlights
Despite advances in our basic understanding of breast cancer biology, the relative contribution of sociocultural and biological factors in breast cancer disparities has remained an area of active debate during the past 30 years, and pure biological, social, and care access–based models cannot accurately describe all epidemiological phenomena.[1,2] Evidence of social drivers of race-based disparities has been demonstrated with respect to screening, stage at detection, treatment, and overall survival.[3,4,5,6] Poverty is associated with advanced-stage disease presentation,[7] and increased distance to care is associated with decreased use of adjuvant therapy.[8]
In the SEER-Medicare cohort, factors associated with increased breast cancer–specific (BCS) mortality included symptomatic detection, advanced disease stage (HR for stage III, 2.33 [95% CI, 1.41-3.85]), and high-grade disease (HR, 1.85 [95% CI, 1.46-2.34])
The molecular cohort of 130 cases with luminal A/B cancer further revealed increased all-cause mortality associated with genomic upregulation of transforming growth factor β activation and p53 dysregulation and decreased mortality associated with androgen receptor, macrophage, cytotoxicity, and Treg signaling
Summary
Despite advances in our basic understanding of breast cancer biology, the relative contribution of sociocultural and biological factors in breast cancer disparities has remained an area of active debate during the past 30 years, and pure biological, social, and care access–based models cannot accurately describe all epidemiological phenomena.[1,2] Evidence of social drivers of race-based disparities has been demonstrated with respect to screening, stage at detection, treatment, and overall survival.[3,4,5,6] Poverty is associated with advanced-stage disease presentation,[7] and increased distance to care is associated with decreased use of adjuvant therapy.[8]. To better understand breast cancer disparities, investigations of “nature and nurture”[17] must be combined, accounting for population sciences and dissemination of cancer care.[18] Most breast cancer research addresses basic science, health services, or clinical domains, but rarely all 3. A key driver of this siloed research is the paucity of population-level linkage containing both clinical and health services data with physical tumor samples. Most genomically analyzed tumor samples are collected in academic medical centers or within the context of a clinical trial, settings known to differ substantially from the general population with respect to patients, treatment, and outcomes.[19,20,21,22]
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