Abstract 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. Also, high levels of TILs is associated with greater likelihood of pathologic complete response (pCR) in response to neoadjuvant treatment (NAT). Previous studies showed that all breast tumors from Asian Americans (AA) and Native Hawaiians and Pacific Islanders (NHPI) patients have a higher percent of sTILs compared to tumors from White patients. Although AAs have a lower cancer death ratio at 0.58, NHPIs have a higher cancer death rate ratio at 1.21 compared to White patients. Our study aims to molecularly characterize the tumor microenvironment in the AA and NHPI populations of patients with TNBC who received NAT. Methods: A retrospective chart review was conducted on 12 AA and 12 NHPI patient cases with early stage TNBC from 2015 to 2022 from a medical oncology clinic within the Hawai’i Pacific Health system. Breast cancer patient data collected included: age at diagnosis, histology, clinical stage, body mass index (BMI), sTILs, pCR, residual cancer burden, and NAT. Pre-treatment core biopsy samples were processed and gene expression profiles analyzed using the NanoString nCounter® Breast Cancer 360™ Panel and the nSolver Advanced Analysis Module. Differentially expressed genes (DEGs) and pathway analyses were generated using the ROSALIND® bioinformatics software. Results: Both AAs (66.7%) and NHPIs (58.3%) had a majority of the basal immunosuppressed (BLIS) TNBC subtype. When we compared TNBC tumors from AA and NHPI patients, 29 DEGs were statistically significant (p0.05, adjusting for age) and the immune cell profiles revealed that NHPI tumors were observed to have fewer monocytes compared to AA tumors (p0.05). When we compared the AA responders and nonresponders to NAT, 68 DEGs were statistically significant and the pathways involved in interleukin-2 signaling and B-cell activation were identified as significant (p0.05, adjusting for age). In the immune cell profile analysis, AA responders expressed more CD8+ T-cells, memory B cells, and resting dendritic cells compared to AA nonresponders (p0.05). When the NHPI responders and nonresponders to NAT were compared, 105 DEGs were statistically significant and the pathways associated with allograft rejection, PD-1 signaling, and antigen processing and presentation were identified as significant (p0.05, adjusting for age). The immune profile analysis revealed no differences. When all responders and nonresponders to NAT were compared, 140 DEGs were statistically significant, and the pathways associated with allograft rejection and PD-1 signaling were identified as significant (p0.05, adjusting for age). The immune profile analysis revealed no differences. Conclusions: In this pilot study, we characterized the gene expression profiles of tumors from AA and NHPI patients with TNBC. Among the two races, there were differences with DEGs but not in pathways. Meanwhile, AA and NHPI responders and nonresponders to NAT had differences in DEGs and biological pathways among the two population groups, suggesting that there may be differences in the biological response to NAT among AA and NHPI. In addition, all responders to NAT had pathways associated with differences in immune response compared to all nonresponders, suggesting that the immune response plays a role in the TME and in different biological mechanisms for the patient’s response to NAT. Future analysis will involve a larger cohort of samples with additional analysis of the TME. We hope to integrate our findings to guide NAT for multiethnic patients. Citation Format: E. T. Nguyen, S. Cheng, M. William, C. Chang, B. Nguyen, V. Khadka, Y. Deng, L. W. Loo, X. Wang, J. A. Fukui. Tumor Microenvironment in Asian-American and Native Hawaiian/Pacific Islander Women With Triple Negative Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-13-02.
Nguyen et al. (Tue,) studied this question.