PROJECT SUMMARY Inflammatory breast cancer (IBC) is the most lethal and aggressive type of breast cancer, with limited therapeutic options. Racial/ethnic disparities have been well documented in patients with IBC. IBC is found in a higher proportion of Native Hawaiian and Pacific Islander (NHPI) women with breast cancer, and their prognosis is poorer than other racial/ethnic populations in Hawaii. Given IBC's aggressiveness and its limited treatment options, there is a critical need to examine the underlying biological mechanisms contributing to the disparities in risks and outcomes for NHPI women with IBC, and to identify molecular targets to improve their treatment options. In this project supplement, we will extend our R01-funded investigations of IBC-relevant mechanisms in the tumor microenvironment (TME), by characterizing the molecular profiles of IBC tumors from NHPI, Asian American and White IBC patients. We propose 2 aims: Aim 1: Characterize the transcriptomic profiles of IBC tumors from NHPI, Asian American, and White patients to examine for differences in tumor biology across the populations. We hypothesize that there are underlying differences in the tumor biology in IBC tumors from NHPI that are associated with the observed disparate risk and outcome for NHPI IBC patients when compared to Asian American and White IBC patients. To test our hypothesis, we will perform RNA sequencing (RNA-seq) for IBC patient tumor samples from The Hawaii Tumor Registry Residual Tissue Repository with a focus on tumors from NHPI, Asian American, and White patients. We will examine for differences in gene expression profiles between NHPI and non-NHPI (Asian American and White) IBC patients. Aim 2: Characterize the immune tumor microenvironment profiles of IBC tumors from NHPI, Asian American, and White patients to examine for differences across the populations. We hypothesize that there are immunological differences in TME of IBC tumors from NHPI patients when compared to IBC tumors from Asian American and White patients. We will conduct multiplexed immunofluorescence staining (mIF) to assess the immune cell composition and the spatial distribution in tissues from NHPI, Asian American, and White patients. We will use the immunological profiles to examine the differences in the tumor immune microenvironment of IBC tumors between NHPI and non-NHPI (Asian American and White) IBC patients. Upon completion, we expect to characterize racial/ethnic differences in the transcriptomic and immune microenvironment landscape of IBC patients. We also expect to determine the expression of key molecules and TME components identified in the parent R01, and how they differ in these three-specific racial/ethnic cohorts of IBC patients. If successful, our supplement will provide insights to identify molecules and TME components associated with the aggressiveness of IBC. They could lead to the identification of therapeutic targets for IBC patients from specific racial or et...