Immune Microenvironments and Hepatocyte Growth Factor Signaling Interactions in Breast Cancer Disparities

Black women suffer disproportionately from higher mortality rates of breast cancers (BC) compared to White women. A driving force in patient outcome is the type of cancer diagnosis and the available treatment options. We focus on two highly aggressive BC subtypes: the hormone receptor negative basal-like breast cancer (BLBC) and the under-studied and deadly inflammatory breast cancer (IBC). Black women present with higher rates of

BLBC vs. White women, and since highly effective therapies are lacking, survival is poor. The NCI states IBC is more common and diagnosed in younger Black women, and is often hormone receptor negative. Clearly a need to conduct more advanced studies into these lethal BCs, and their common themes, is critical for patient survival and understanding disparate outcomes. Many studies assessing differences in BCs in Black women and White women examine tumor characteristics; however, etiologic factors that lead to this disparity remain poorly defined. Our data show Black women have unique immune and stromal cell infiltrate and altered protein levels within normal breast and tumor microenvironments. Our objective is to identify mechanisms involved in the progression of aggressive, metastatic BC in Black women as a consequence of stromal effects at the site of the cancerous lesion.

Project Aims:

1. Use CBCS samples and data to evaluate HGF signaling as a mechanism of BLBC and IBC BC progression in Black versus White patients.

2. Evaluate current HGF gene signature and identified EMT IBC-specific gene signatures in CBCS and assess their contributions to IBC pathogenesis and whether these signatures are significantly associated with poor outcomes and race.

3. Characterize the role of mutated DATE and HGF signaling on genomic instability in BLBC and IBC.

Our long-term goals are to determine the role of HGF function in BLBC and IBC and its contribution to BC disparities. To define new biomarkers for BLBC and IBC that will identify subsets of patients who may benefit the most from existing HGF/MET therapies and new therapeutic strategies.