Do neighborhood-level disparities in breast cancer–specific survival remain after accounting for individual, tumor, and treatment characteristics?

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The screening, treatment, and survival in breast cancer cases have improved considerably, but differences in survival outcomes persist, especially in disadvantaged neighborhoods.

A recent JAMA Network Open study assessed the role of neighborhood-level disparities in determining shorter breast cancer-specific survival after accounting for several confounding factors related to the tumor, individual, and treatment characteristics.

Study: Neighborhood Disadvantage and Breast Cancer–Specific Survival in the US. Image Credit: Gorodenkoff/Shutterstock.comStudy: Neighborhood Disadvantage and Breast Cancer–Specific Survival in the US. Image Credit: Gorodenkoff/Shutterstock.com

Background

Neighborhoods are complex environments with distinct physical, cultural, and economic attributes. Communities facing economic challenges may have limited access to essential health services, including facilities for screening, mammography, and treatment. This lack of resources can affect breast cancer survival rates in these areas.

Research has shown the association between neighborhood disadvantage and breast cancer survival, even after controlling for many of the neighborhood-level, individual-level, and structural factors.

This suggests the presence of some unaccounted underlying mechanisms which have not been explored yet. Most prior research has focussed on specific geographic areas or subsets of the population, which has limited its generalizability.

About this study

This study used a robust index of neighborhood disadvantage (Yost index) to assess the association between neighborhood disadvantage and breast cancer-specific and overall survival post-controlling for tumor, individual, and treatment factors in a national cohort. The null hypothesis was the presence of survival disparities post-adjustment for confounders.

The cohort comprised patients who were diagnosed with breast cancer from 2013 to 2018 and were sourced from the data held by the National Cancer Institute. The main exposure measure was the neighborhood disadvantage, captured by Yost index quintiles. The main outcome variable was breast cancer-specific survival.

This was measured using a cause-specific hazard model controlling. Several factors were controlled for, including race, stage, rurality, age, ethnicity, insurance, subtype, and receipt of treatment.

Study findings

It was noted that patients in the most disadvantaged neighborhoods reported shorter breast cancer-specific and overall survival rates. This association prevailed even after adjusting for treatment characteristics that are commonly used to explain survival differences.

This suggests the presence of unaccounted-for non-biological or biological mechanisms through which breast cancer-specific survival is influenced by neighborhood disadvantage.

The findings raise an important question regarding whether neighborhood disadvantage could give rise to more malignant tumor biology and low survival rates.

In social genomics studies, psychological and biological stress has been associated with neighborhood disadvantage. These stresses lead to upregulating stress-related neuroendocrine signaling pathways by placing demands on the sympathetic nervous system.

The signaling pathways lead to a gene expression called conserved transcriptional response to adversity (CTRA). Research has associated the CTRA gene expression with upregulation of proinflammatory gene expression.

This, in turn, facilitates a prometastatic environment, suggesting aggressive tumor biology. Therefore, this is how breast cancer survival could be affected by neighborhood disadvantage. It must be noted that more research is needed to closely examine the association between the CTRA gene, tumor expression, and neighborhood disadvantage in humans.

Non-Hispanic Black patients were seen to have the highest mortality risk relative to non-Hispanic White and Hispanic patients. This is indicative of the fact that social determinants of health were not fully controlled for.

For the relative risk of triple-negative breast cancer (TNBC), similar results were noted when contrasted with human epidermal growth factor receptor two negative (ERBB2−) disease.

It was also mentioned that unaccounted-for non-biologic pathways could also be driving the persistent disparities in breast cancer-specific survival.

The immeasurable effects of structural racism, financial burden, and trust on healthcare practitioners could all drive inequities in survival. Future research should appropriately account for these factors.

Conclusions

In sum, neighborhood disadvantage was noted to be independently associated with shorter survival in breast cancer patients despite accounting for tumor characteristics, individual-level factors, and treatment.

In order to understand these residual disparities better, future research should consider the components of the built environment, which could influence outcomes.

In this regard, a translational epidemiologic approach could be the way forward. This could consider neighborhood disadvantages when devising cancer control interventions and risk-stratifying vulnerable populations.

In this way, the translational epidemiologic approach could advance precision medicine in oncology.

Similar to previous retrospective observational studies, this study also has certain limitations. Information on comorbidities, medicine doses, treatment rationale, and completion of radiotherapy and chemotherapy could not be obtained.

Another limitation concerns the important issue of access to care. Individual insurance coverage was used as a proxy for access to care; however, this is an incomplete representation of all access to care measures.

Journal reference:
Dr. Priyom Bose

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.

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