Women of African descent have the highest breast cancer mortality in the United States and are more likely than women from other population groups to develop an aggressive disease. It remains uncertain to what extent breast cancer in Africa is reminiscent of breast cancer in African American or European American patients. Here, we performed whole-exome sequencing of genomic DNA from 191 breast tumor and non-cancerous adjacent tissue pairs obtained from 97 African American, 69 European American, 2 Asian American, and 23 Kenyan patients. Our analysis of the sequencing data revealed an elevated tumor mutational burden in both Kenyan and African American patients, when compared with European American patients. TP53 mutations were most prevalent, particularly in African American patients, followed by PIK3CA mutations, which showed similar frequencies in European American, African American, and the Kenyan patients. Mutations targeting TBX3 were confined to European Americans and those targeting the FBXW7 tumor suppressor to African American patients whereas mutations in the ARID1A gene that are known to confer resistance to endocrine therapy were distinctively enriched among Kenyan patients. A Kyoto Encyclopedia of Genes and Genomes pathway analysis could link FBXW7 mutations to an increased mitochondrial oxidative phosphorylation capacity in tumors carrying these mutations. Finally, Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures in tumors correlated with the occurrence of driver mutations, immune cell profiles, and neighborhood deprivation with associations ranging from being mostly modest to occasionally robust. To conclude, we found mutational profiles that were different between these patient groups. The differences concentrated among genes with low mutation frequencies in breast cancer. Significance: The study describes differences in tumor mutational profiles between African American, European American, and Kenyan breast cancer patients. It also investigates how these profiles may relate to the tumor immune environment and the neighborhood environment in which the patients had residence. Finally, it describes an overrepresentation of ARID1A gene mutations in breast tumors of the Kenyan patients.

Neighborhood conditions are dynamic; the association of changing neighborhood socioeconomic factors with cancer preventive behaviors remains unclear. We examined associations of neighborhood socioeconomic deprivation, gentrification, and change in income inequality with adherence to the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention in The Hispanic Community Health Study/Study of Latinos (HCHS/SOL). The HCHS/SOL enrolled 16,415 adults, ages 18–74 years, at baseline (2008–2011), from communities in the Bronx, NY, Chicago, IL, Miami, FL, and San Diego, CA. Geocoded baseline addresses were linked to the 2000 decennial Census and 5-year American Community Survey (2005–2009 and 2012–2016) tracts to operationalize neighborhood deprivation index (NDI), gentrification, and income inequality. Complex survey multinominal logistic regression models estimated the relative risk ratio (RRR) with overall guideline adherence level (low, moderate, high) and by components—diet, physical activity, body mass index (BMI), and alcohol intake. Overall, 14%, 60%, and 26% of the population had low, moderate, and high ACS guideline adherence, respectively. NDI was negatively associated with risk of high (vs. low) guideline adherence [RRR = 0.87, 95% confidence interval (CI) = 0.78–0.98], although attenuated after controlling for individual socioeconomic status (SES; RRR = 0.89, 95% CI = 0.80–1.00), and associated with lower adherence to BMI recommendations (low vs. moderate RRR = 0.90, 95% CI = 0.84–0.97; high RRR = 0.86, 95% CI = 0.77–0.97). Gentrification was associated with higher likelihood of meeting the dietary recommendations (low vs. moderate RRR = 1.04, 95% CI = 1.01–1.07), but not with overall adherence or individual components. Change in income inequality was not associated with outcomes. Neighborhood deprivation may be negatively associated with ACS guideline adherence among Hispanic/Latino adults. Significance: This study provides new evidence on the link between neighborhood gentrification, changing income inequality and adoption and maintenance of cancer preventive behaviors in an understudied population in cancer research. We observed that while neighborhood deprivation may deter from healthy lifestyle behaviors, positive changes in neighborhood SES via the process of gentrification, may not influence lifestyle guideline adherence among Hispanic/Latino adults.

Structural racism has been identified as a fundamental cause of health disparities. For example, racial, ethnic, and economic neighborhood segregation; concentrated poverty; community disinvestment; and sociocultural context influence obesity and cancer disparities. Effects of structural racism are also evident through neighborhood obesogenic conditions such as limited access to affordable and healthy foods and physical activity opportunities within segregated communities that contribute to obesity and obesity-related cancer disparities. This article describes and expands on cross-cutting themes raised during a webinar held by the National Cancer Institute (NCI): (1) how structural factors, including neighborhood segregation and obesogenic conditions within racial and ethnic disadvantaged communities, influence disparities in the United States; (2) current research challenges and best ways to address them; and (3) selected priorities of the NCI aimed at addressing multilevel and intersecting factors that influence obesity-related cancer disparities. Further research is needed to understand how residential segregation and neighborhood obesogenic conditions influence cancer prevention and control across the continuum. Identifying the best approaches to address obesity and cancer disparities using social determinants of health framework and community-engaged approaches guided by a structural racism lens will allow researchers to move beyond individual-level approaches.