Among US women, breast cancer is the leading cancer diagnosis, with 1 in 8 women expected to receive a breast cancer diagnosis in their lifetime.¹ Approximately 15-20% of all breast cancers are classified as triple negative breast cancer (TNBC).² Breast tumors with this classification are called triple negative because they do not express any of the three receptors (estrogen, progesterone, or human epidermal growth factor receptor 2) used to determine molecular subtypes. Although not the most prevalent subtype, TNBC is among the most aggressive. Compared to other breast cancer subtypes, women with TNBC are more likely to be diagnosed at later stages and die from the disease due to few treatment options.¹ Incidence of TNBC is not distributed equally by race. Rather, TNBC incidence is 2-3 times higher among Black women compared to other racial and ethnic groups.¹ Higher TNBC incidence among Black women contributes, in part, to observed racial disparities in breast cancer mortality, where Black women are 38% more likely than White women to die from the disease.¹ With poor tumor characteristics, limited treatment options, and reduced survival, it is necessary to understand disease development so that TNBC can be prevented, particularly in vulnerable populations, including Black women.

Understanding the context within which individuals live is important for elucidating disease occurrence and may be relevant to TNBC development. Because individuals spend extended time in their residential communities, the neighborhood environment has been investigated as an influential contextual factor that may impact health and well-being.³ The socioeconomic neighborhood environment, often captured through neighborhood deprivation or socioeconomic status (SES) indices, is one of the most studied aspects of the neighborhood environment. Living in a deprived neighborhood can profoundly shape health by influencing socioeconomic opportunities and mobility, access to educational and healthcare resources, and the ability to practice healthy behaviors,^3,4 all of which may play a role in breast cancer development. Research on neighborhoods demonstrates that the distribution of adverse neighborhood attributes is socially patterned, such that racially minoritized individuals are more likely to live in deprived neighborhoods.⁵ The co-location of race and neighborhood deprivation suggests that neighborhoods may contribute to racial disparities in health.⁵ In fact, poor neighborhood environments are hypothesized to contribute to observed racial disparities in breast cancer, particularly disparities in the distribution of TNBC by race.¹ However, how neighborhood deprivation operates and its impact on health, specifically breast cancer, may vary by geographic characteristics, such as rurality.⁶ Urban and rural environments may have unique attributes or challenges (e.g., accessibility, isolation) that interact with neighborhood deprivation.⁷ Investigation of neighborhood deprivation and TNBC in the context of race and rurality could provide a more complete understanding of TNBC development and racial disparities.

Prior literature on the relationship between neighborhood deprivation indices and TNBC suggests that living in a deprived environment may be associated with an increased occurrence of TNBC.^8-12 However, there is inconsistency in the literature, with some studies reporting no association between neighborhood deprivation and TNBC.^13-15 Few studies have reported on the neighborhood deprivation-TNBC association among Black women,^10,12,13 who are more likely to live in deprived neighborhoods.¹⁶ Among these studies, non-significant positive and null associations have been observed.^10,12,13 Furthermore, to our knowledge, no study has considered the relationship between neighborhood deprivation and TNBC in the context of rurality. Thus, the objective of this study was to build on prior research by further disentangling the complex relationships between race, place, and TNBC. To do this, we examined the associations between neighborhood deprivation and TNBC, as well as other breast cancer subtypes, according to race, rurality, and their intersection.

Overall, the average age of patients at diagnosis was 60.2 (standard deviation=13.2) years, 31.5% were NHB, and 23.8% lived in a rural county (Table 1). Of the 40,095 women in the study population, 5,328 (13.3%) were diagnosed with TNBC, 1,926 (4.8%) with HER2-enriched, 4,958 (12.4%) with luminal B, and 27,883 (69.5%) with luminal A breast cancer. Women living in the most deprived neighborhoods (Q5) were more likely to be NHB, single, have Medicaid insurance, have stage III or IV breast cancer, and live in persistent poverty compared to those living in the least deprived neighborhoods (Q1). Patient characteristics at diagnosis according to NDI and race are shown in Supplemental Table 1.

In this study of NHB and NHW breast cancer patients in Georgia, we found that living in neighborhoods with the highest versus lowest deprivation index was associated with a 33% increased odds of TNBC versus luminal A breast cancer. This association was observed among NHB and NHW women; however, the association was weaker among NHB women. The neighborhood deprivation-TNBC association was present among women living in urban and rural counties, suggesting no effect measure modification by rurality. Nevertheless, we observed a weaker association among patients from urban settings. In addition to TNBC, neighborhood deprivation was also associated with increased odds of HER2-enriched versus luminal A breast cancer, which was confined to NHW women living in urban counties. A neighborhood deprivation-luminal B breast cancer association was observed only in rurality-stratified analyses, with women, especially NHW women, residing in urban counties exhibiting elevated odds of the disease relative to luminal A breast cancer. Observed findings from this study indicate that neighborhood deprivation may be relevant to the development of aggressive forms of breast cancer.

Results from the present analysis align with several studies that have examined the impact of adverse neighborhood attributes on breast cancer subtypes. For example, among prior studies that measured neighborhood deprivation via a multidimensional index similar to that used in the current analysis, most,^8-12 but not all,^13-15 reported neighborhood deprivation to be associated with a 12%-95% increase in the occurrence of TNBC. The magnitude of association observed in the present analysis is consistent with previously reported estimates. Prior studies assessing ER− breast cancer, which includes TNBC cases, also demonstrate positive associations between neighborhood deprivation and the development of aggressive breast cancer.^20-22 Moreover, other neighborhood characteristics, which likely correlate with neighborhood deprivation indices (e.g., median household income, index of concentration at the extremes), have been associated with TNBC occurrence,^23-28 suggesting a role of adverse neighborhood attributes in TNBC development. Consistent with our results, prior research also indicates that exposure to deprived neighborhoods may be associated with the HER2-enriched subtype, with most,^9-11,23,25 although not all,^13,24 studies reporting positive associations. Fewer studies have examined neighborhood deprivation relative to luminal B breast cancer. These studies show inconsistent data, as positive^11,13,25 and null associations^9,23,24 have been reported. Thus, more research is necessary. Together, results from the present analysis and previous studies suggest that the neighborhood environment may be a useful intervention target to reduce the occurrence of aggressive breast cancer subtypes.

We found neighborhood deprivation was associated with greater odds of TNBC relative to luminal A breast cancer regardless of race. This finding, which aligns with two previous studies investigating median household income and TNBC,^26,28 indicates that aspects of a deprived neighborhood may be harmful for both NHB and NHW women. However, the slightly stronger association among NHW women suggests that the neighborhood environment may be a larger contributor to TNBC development among this racial group as compared with NHB women. The diminishing returns hypothesis could explain the weaker association among NHB women,²⁹ as well as the observed null association between neighborhood deprivation and HER2-enriched breast cancer among NHB women. Based on the diminishing returns hypothesis, living in an affluent neighborhood may not afford Black women the same benefits and resources as it does White women, leading to a smaller social gradient or differential between Black women in the most versus the least deprived neighborhoods.²⁹ In one study examining median household income and TNBC, a more pronounced association was found among NHB compared to NHW women.²⁸ A second study reported similar effect estimates among both racial groups.²⁶ Further research is needed to understand the impact of neighborhood deprivation on TNBC by race. Nonetheless, the positive neighborhood deprivation-TNBC association observed among Black women in the present and previous studies,^10,12,26,28 coupled with the fact that Black women are more likely to live in deprived neighborhoods, indicates that neighborhood deprivation may contribute to racial disparities in TNBC.

Because neighborhood deprivation may manifest differently in urban versus rural areas,⁷ we assessed the neighborhood deprivation-breast cancer subtype associations according to rurality. Stratified analyses revealed no effect measure modification for TNBC-specific results which may suggest that the negative influence of neighborhood deprivation on TNBC operates similarly in urban and rural environments. In contrast, associations for HER2-enriched and Luminal B breast cancer were only observed among women, particularly NHW women, living in urban counties. To our knowledge, no previous study has evaluated the neighborhood deprivation-breast cancer subtype associations by rurality. Future research should conduct rurality-specific analyses to confirm our findings.

The neighborhood environment could influence the development of breast cancer, and TNBC in particular, through multiple mechanisms. From a behavioral perspective, neighborhood deprivation could limit residents’ ability to practice healthy behaviors. For example, individuals living in deprived neighborhoods have limited access to high-quality education, high-paying jobs, healthy food stores, and green spaces, and fewer opportunities for physical activity, which could increase the risk of obesity.⁴ Some studies have reported associations between unhealthy diets and TNBC or ER− breast cancer,^30,31 and evidence linking obesity to aggressive breast tumor biology is accumulating.³² Collectively, these unfavorable conditions can hinder individuals’ ability to acquire the knowledge, resources, and nutrition necessary to build, practice, and maintain a healthy lifestyle, which could, in turn, impact breast cancer development. From a biological perspective, exposure to neighborhood deprivation could lead to cellular and molecular changes that may be relevant to TNBC development.³³ For instance, in addition to the unfavorable neighborhood conditions described above, deprived neighborhoods also tend to have more crime activity and greater social disorder.⁴ As a result, residents may feel unsafe, have less social control, and have reduced ability to create social ties with their neighbors.⁴ Long-term exposure to adverse neighborhood social conditions could lead to chronic psychosocial stress and overactivation of the sympathetic nervous system and hypothalamic pituitary adrenal axis, the fight or flight response.^4,33 Hormones released during the stress response can suppress the immune system and increase inflammation, creating an environment conducive for breast cancer development. Inflammatory pathways are likely implicated in the development of all breast cancers,³⁴ but they may be more relevant for TNBC since the greatest mechanistic component for hormone receptor-positive tumors are hormonal pathways and more inflammatory activity has been observed in TNBC compared to non-TNBC subtypes.³⁵ In addition, neighborhood deprivation and adverse neighborhood characteristics have been associated with increased methylation of genes related to inflammatory and stress pathways.^36,37 These DNA methylation patterns may be particularly relevant for aggressive forms of breast cancer.³⁷ Thus, the neighborhood environment could influence the development of breast cancer subtypes through multiple biological and behavioral pathways.

Given these biological and behavioral pathways, neighborhoods may be a viable intervention target to reduce breast cancer development, particularly development of aggressive subtypes. Neighborhoods are complex and multifaceted, as reflected in our multidimensional NDI composite measure. Therefore, intervention strategies that incorporate a multipronged approach to address multiple neighborhood domains may be necessary to produce the greatest impact and counteract the harmful influence of neighborhood deprivation. Furthermore, neighborhood reinvestment or revitalization strategies that seek to improve neighborhood schools and educational support services, attract quality businesses, which can bring new job opportunities, income, and resources to residents, improve housing conditions, enhance the built environment, and reduce crime could positively impact the socioeconomic landscape of the neighborhood environment. This, in turn, could improve residents’ overall health and potentially reduce the risk of developing aggressive breast cancer subtypes. A longitudinal study of neighborhood reinvestment demonstrated that neighborhood improvements were associated with reduced food insecurity, lower stress, and increased neighborhood safety and satisfaction.³⁸ As noted above, some of these outcomes represent mechanisms through which neighborhood deprivation may influence breast cancer subtypes; thus, providing further support for leveraging the neighborhood environment as a potential intervention target.

While there are strengths of the present analysis, including its large sample size, comprehensive multidimensional measurement of neighborhood deprivation, and examination of race and rurality as effect modifiers, there are also limitations that warrant discussion. The current analysis has a cross-sectional study design, as neighborhood deprivation and hormone receptor status were measured at diagnosis. The cross-sectional nature limits our ability to make inferences regarding disease etiology. We did not have data on patients’ residential histories or housing tenure. Therefore, we were unable to assess exposure status at time points prior to diagnosis. Our single measurement of neighborhood deprivation may not reflect patients’ exposure during critical time windows for cancer development or capture cumulative exposure. However, research on residential history and mobility shows that women tend to live in and move to similar neighborhood environments throughout their lifetime.³⁹ In this analysis, we derived a multidimensional measure of neighborhood deprivation to summarize various aspects of the socioeconomic neighborhood environment. However, neighborhoods can be characterized by more than just socioeconomic conditions. For example, the food, retail, built, social, and physical environments within a neighborhood can influence residents’ behaviors, access to resources and healthcare, and stress, all of which may play a role in the development of different breast cancer subtypes. While we did not include these other neighborhood conditions, they correlate with neighborhood deprivation. Hormone receptor status, which was based on ER, PR, and HER2 biomarker data collected by the GCR, was used to define breast cancer subtypes in this study. In addition to hormone receptor status, other information, such as data on Ki67—a marker of tumor cell proliferation—is also necessary to accurately classify breast cancers into disease subtypes.⁴⁰ Ki67 data was not available. Thus, we could not confirm breast cancer subtypes. Unmeasured confounding may exist, as we did not have data on individual-level characteristics or breast cancer risk factors, such as individual-level SES and reproductive factors. Nevertheless, previous studies have observed associations between neighborhood deprivation and TNBC, even after adjusting for individual-level factors.^10-12 Lastly, the present study was conducted among NHB and NHW breast cancer patients residing in Georgia. The generalizability of our findings to other racial and ethnic groups and geographic areas may, therefore, be limited. However, similar associations have been reported among Hispanic populations⁹ and individuals living outside of Georgia.^8-11

In this study of neighborhood deprivation and breast cancer subtypes among NHB and NHW women, living in a deprived neighborhood was associated with increased odds of TNBC, regardless of race and rurality, and HER2-enriched breast cancer among NHW women and women residing in urban counties. Findings from this study support the role of adverse neighborhood characteristics in the occurrence of aggressive breast cancer subtypes. Moreover, the observed neighborhood deprivation-TNBC association among NHB women suggests that neighborhood deprivation may contribute to racial disparities in TNBC, given that Black women are more likely than White women to live in deprived neighborhoods.¹⁶ Based on these findings, neighborhood-level interventions may help reduce breast cancer occurrence and mitigate racial disparities in TNBC.