Impact of Neighborhood Disadvantage on High-Risk Oncotype DX Recurrence Scores and Breast Cancer Survival

Goel, Neha; Hernandez, Alexandra; Kwon, Deukwoo; Antoni, Michael H.; Cole, Steve

doi:10.1097/sla.0000000000006082

Cited by 3 publications

(1 citation statement)

References 54 publications

(118 reference statements)

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“…11 For instance, studies evaluating structural racism through measures of socioeconomic and neighborhood disadvantage have demonstrated that greater neighborhood level deprivation is associated with more aggressive breast cancer subtypes and unfavorable tumor genomics. [22][23][24][25] This study is limited by its retrospective design. Likewise, our results are limited by the variables provided through SEER.…”

Section: Discussionmentioning

confidence: 99%

Racial disparities in disease‐specific mortality and surgical management of patients with ductal carcinoma in situ with microinvasion

Chen,

Handley,

Elsaid

et al. 2024

Journal of Surgical Oncology

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Background and ObjectivesGiven persistent racial disparities in breast cancer outcomes, this study explores racial differences in disease‐specific mortality and surgical management among patients with microinvasive ductal carcinoma in situ (DCIS‐MI).MethodsThe Surveillance, Epidemiology, and End Results Program was queried for patients aged 18+ years with DCIS‐MI between January 1, 2010 and December 31, 2018. The study cohort was divided into non‐Hispanic Black (NHB) and non‐Hispanic White (NHW) patients. Disease‐specific mortality was evaluated using Cox proportional hazards models.ResultsA total of 3400 patients were identified, of which 569 (16.7%) were NHB and 2831 (83.3%) were NHW. Compared with NHW patients, NHB patients had more positive lymph nodes (7.6% vs. 3.9% p < 0.001). In addition, NHB women were more likely to undergo axillary lymph node dissection (6.0% vs. 3.8%, p = 0.044) and receive chemotherapy (11.8% vs. 7.2%, p < 0.001). There were no racial differences in breast surgery type (p = 0.168), reconstructive surgery (p = 0.362), or radiation therapy (p = 0.342). Overall, NHB patients had worse disease‐specific mortality (adjusted hazard ratio 2.13, 95% confidence interval [CI]: 1.10–4.14) with mortality risks diverging from NHW women after 3 years (6 years rate ratio [RR] 2.12, 95% CI: 1.13–4.34; 9 years RR 2.32, 95% CI: 1.24–4.35).ConclusionsNHB women with DCIS‐MI present with higher nodal disease burden and experience worse disease‐specific mortality than NHW women.

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Section: Discussionmentioning

confidence: 99%

Racial disparities in disease‐specific mortality and surgical management of patients with ductal carcinoma in situ with microinvasion

Chen,

Handley,

Elsaid

et al. 2024

Journal of Surgical Oncology

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ZIP Code to Genomic Code

Goel,

Hernandez,

Antoni

et al. 2024

Annals of Surgery

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Objective: To determine the association between objective (geospatial) and subjective (perceived) measures of neighborhood disadvantage (ND) and aggressive breast cancer (BCa) tumor biology, defined using validated social adversity-associated transcription factor (TF) activity and clinical outcomes. Summary Background Data: ND is associated with shorter BCa recurrence-free survival (RFS), independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which ND influences RFS. Methods: We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on protocol. Covariate-adjusted multivariable regression analyzed objective and subjective ND scores with 5 validated TFs of social adversity and aggressive biology—pro-inflammatory activity (NF-kB, AP-1), sympathetic nervous system (SNS) activity (CREB), and protective cellular responses (IRF, STAT). To clinically validate these TFs as prognostic biomarkers of aggressive biology, logistic regression and multivariable Cox proportional-hazards models analyzed their association with Oncotype DX scores and RFS, respectively. Results: Increasing objective ND was associated with aggressive tumor biology (up-regulated NF-kB, AP-1, down-regulated IRF, STAT) and SNS activation (up-regulated CREB). Increasing subjective ND (e.g., threat to safety), was associated with up-regulated NF-kB and CREB and down-regulated IRF. These TF patterns were associated with high-risk Oncotype DX scores and shorter RFS. Conclusions: In the largest human social genomics study, objective and subjective ND were significantly associated with TFs of aggressive biology and SNS activation. These TFs also correlated with worse clinical outcomes, implicating SNS activation as one potential mechanism behind ND survival disparities. These findings remain to be validated in a national cohort.

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Social Genomic Determinants of Health: Understanding the Molecular Pathways by Which Neighborhood Disadvantage Affects Cancer Outcomes

Goel,

Hernandez,

Cole

2024

JCO

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PURPOSE Neighborhoods represent complex environments with unique social, cultural, physical, and economic attributes that have major impacts on disparities in health, disease, and survival. Neighborhood disadvantage is associated with shorter breast cancer recurrence-free survival (RFS) independent of individual-level (race, ethnicity, socioeconomic status, insurance, tumor characteristics) and health system-level determinants of health (receipt of guideline-concordant treatment). This persistent disparity in RFS suggests unaccounted mechanisms such as more aggressive tumor biology among women living in disadvantaged neighborhoods compared with advantaged neighborhoods. The objective of this article was to provide a clear framework and biological mechanistic explanation for how neighborhood disadvantage affects cancer survival. METHODS Development of a translational epidemiological framework that takes a translational disparities approach to study cancer outcome disparities through the lens of social genomics and social epigenomics. RESULTS The social genomic determinants of health, defined as the physiological gene regulatory pathways (ie, neural/endocrine control of gene expression and epigenetic processes) through which contextual factors, particularly one's neighborhood, can affect activity of the cancer genome and the surrounding tumor microenvironment to alter disease progression and treatment outcomes. CONCLUSION We propose a novel, multilevel determinants of health model that takes a translational epidemiological approach to evaluate the interplay between political, health system, social, psychosocial, individual, and social genomic determinants of health to understand social disparities in oncologic outcomes. In doing so, we provide a concrete biological pathway through which the effects of social processes and social epidemiology come to affect the basic biology of cancer and ultimately clinical outcomes and survival.

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Impact of Neighborhood Disadvantage on High-Risk Oncotype DX Recurrence Scores and Breast Cancer Survival

Cited by 3 publications

References 54 publications

Racial disparities in disease‐specific mortality and surgical management of patients with ductal carcinoma in situ with microinvasion

Racial disparities in disease‐specific mortality and surgical management of patients with ductal carcinoma in situ with microinvasion

ZIP Code to Genomic Code

Social Genomic Determinants of Health: Understanding the Molecular Pathways by Which Neighborhood Disadvantage Affects Cancer Outcomes

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