Body composition and breast cancer survival: immune and metabolic biomarkers in breast tumors - Disparities Supplement

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ABSTRACT This Supplement to R01CA251589 “Body composition and breast cancer survival: immune and metabolic biomarkers in breast tumors” responds to the PAR-22-114 “Administrative Supplements to Support Cancer Disparity Collaborative Research.” The long-term goal is to reduce the disproportionate burden of breast cancer mortality experienced by non-Hispanic black (NHB) women by understanding the role of a key, modifiable risk factor: excess adiposity. Preclinical models indicate that excess adiposity impairs anti-tumor immunity and alters metabolic and cell proliferation pathways to promote cancer progression. Given the markedly higher prevalence of obesity (body mass index [BMI] >30-kg/m2) in NHB vs. vs. non-Hispanic white (NHW) women, obesity is assumed to contribute to disparities in survival. Yet, BMI does not consistently predict survival after breast cancer in NHB women or in women hormone receptor negative breast tumors, which are more common in NHB women. Preliminary studies suggest that more specific measures of adipose tissue distribution outperform BMI to predict breast cancer survival. Given racial differences in adipose tissue distribution at a given BMI, there is a need to study body composition to elucidate the role of adiposity in generating racial disparities. This administrative supplement establishes a new collaboration between a cancer disparities expert and a study team with expertise in epidemiology, tumor biology and breast medical oncology. The parent grant seeks to understand how systemic factors such as patient body composition impact the local breast tumor microenvironment and therefore breast cancer survival. With this administrative supplement, we expand those aims to include a disparities focus by comparing NHB vs. NHW women. We will expand representation of tumors from NHB women in our study, and conduct a series of analyses focused on racial disparities. Specifically, we will examine: racial differences in the distribution of visceral v. subcutaneous adiposity and in associations of these adipose tissue depots with survival (Aim 1); racial differences in the associations of each adipose tissue depot with expression of immune and metabolic genes in the breast tumor microenvironment (Aim 2); and racial differences in the associations of immune and metabolic genes in the breast TME with survival (Aim 3). Potential harms of excess adiposity may be mitigated through both medical and lifestyle interventions; thus, understanding the role of adiposity in generating racial disparities in breast cancer is a high priority not only for research but patient care.