Gene expression profiling of the tumor microenvironment in Asian American and Native Hawaiian/Pacific Islander women with triple negative breast cancer.

Abstract

e12622 Background: Triple negative breast cancer (TNBC) accounts for approximately 10-20% of breast cancer cases and has the worst overall survival and prognosis compared to other breast cancer subtypes. A higher percent of stromal tumor infiltrating lymphocytes (sTILs) in the tumor microenvironment (TME) of TNBC correlates with an improved prognosis secondary to the improved efficacy of neoadjuvant treatment. Previous studies showed that breast tumors from Asian American (AA) and Native Hawaiians and Pacific Islander (NHPI) patients have a higher percent of sTILs compared to tumors from White patients. Despite this favorable prognostic tumor feature, NHPI patients have a higher breast cancer mortality rate at 24.9% compared to other races and ethnic groups in Hawai’i. Our study aims to molecularly characterize the tumor microenvironment in a diverse population of patients with TNBC who received neoadjuvant therapy. Methods: A retrospective chart review was conducted on 12 AA and 12 NHPI patients with early stage TNBC from 2015 to 2022 from a medical oncology clinic within the Hawai’i Pacific Health system. Patient data collected include age at diagnosis of breast cancer, histology, clinical stage, BMI, sTILs, pathologic complete response, residual cancer burden and neoadjuvant treatment. Pre-treatment core biopsy samples were processed and analyzed using the NanoString nCounter Breast Cancer 360 Panel. Further analysis was obtained using the nSolver Advanced Analysis Module. Results: Both AAs (66.7%) and NHPIs (58.3%) had a majority of the basal immunosuppressed (BLIS) TNBC subtype. Between AAs and NHPIs, 31 differentially expressed genes (DEGs) were statistically significant (p < 0.05). Among the top 10 genes, AA patients presented with higher expressions of MLPH, FGFR4, TSPAN1, CHAD, CACNG4, BMP4, TNN, and ITGB6, and decreased expressions of IL12RB2 and MYC compared to NHPI patients. In the immune profile analysis, NHPI tumors were observed to have fewer monocytes compared to AA tumors (p < 0.05). Among the subset of AA treatment responders(n = 4) versus nonresponders (n = 8) to neoadjuvant therapy, 33 genes were statistically significant (p < 0.05). Among the top 10 DEGs, AA responders expressed more of HLA-DQA1, HLA-DQB1, BMP7, PTGDS, CXCL9, CD1E, and CD8A, and less of CRYAB, TTYH1, and SLPI. AA responders also expressed more CD8+ T-cells, memory B cells, and resting dendritic cells compared to AA nonresponders (p < 0.05). Conclusions: In this pilot study, we characterized the gene expression profiles of AAs and NHPIs. In AA breast cancer tumors, responders expressed different genes and sTILs compared to nonresponders, suggesting that the TME may play a role in treatment outcomes. Future analysis will involve a larger cohort of samples with additional TME analysis. We hope to integrate our findings to guide neoadjuvant treatment for patients.