Genomic analysis of the tumor microenvironment in Asian and Native Hawaiian and Pacific Islander patients with triple negative breast cancer.

person Edward Nguyen John A. Burns School of Medicine, University of Hawaii Manoa, Honolulu, HI info_outline Edward Nguyen, Shirley Cheng, Connie Chang, Ba Thong Nguyen, Vedbar Khadka, Youping Deng, Jeffrey Killeen, Jami Aya Fukui

Authors person Edward Nguyen John A. Burns School of Medicine, University of Hawaii Manoa, Honolulu, HI info_outline Edward Nguyen, Shirley Cheng, Connie Chang, Ba Thong Nguyen, Vedbar Khadka, Youping Deng, Jeffrey Killeen, Jami Aya Fukui Organizations John A. Burns School of Medicine, University of Hawaii Manoa, Honolulu, HI, University of Hawaii Cancer Center, Honolulu, HI, Kapiolani Medical Center for Women and Children, Honolulu, HI Abstract Disclosures Research Funding NCI P30 5P30CA071789 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 subtypes. Unlike other subtypes, patients with TNBC are responsive to neoadjuvant therapy. A higher percent of stromal tumor infiltrating lymophocytes (sTILs) in the tumor microenvironment of TNBC correlates with an improved prognosis. Previous studies demonstrate that Native Hawaiians and Pacific Islanders (NHPIs) and Asians have equivocal percent of sTILs. Yet NHPIs have a higher mortality rate at 24.9% compared to Asians at 11%. Our study aims to molecularly characterize the tumor microenvironment in a diverse population of patients with TNBC who received neoadjuvant therapy. Methods: Retrospective chart review was conducted on 12 Asians 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, BMI, clinical stage, sTILs, residual cancer burden, neoadjuvant treatment, and pathologic complete response. Core biopsy samples were processed and analyzed using the nCounter Breast Cancer 360 Panel. Further analysis was obtained using the nSolver Advanced Analysis Module. Results: Patient characteristics are listed in the table. Most patients had the basal-like immunosuppressed TNBC subtype. Among differentially expressed genes between races, 31 genes were statistically significant. NHPIs expressed more IL12RB2 and MYC, and Asians expressed more FGFR4 and MLPH. Among responders compared to non-responders, 5 genes were statistically significant. Responders expressed more STC1 and PTGER3, and non-responders expressed more CRAYAB, TMPRSS2, and CHAD. Among old and young patients, 132 genes were statistically significant. Older patients expressed more FUT3 and CKMT1, and younger patients expressed more MMP7 and MIA. Conclusions: In this pilot study, the molecular and genetic differences suggest that the tumor microenvironment may play a role in treatment outcomes between NHPIs and Asians. Further analysis will be conducted to determine the differences in immune cell infiltration. Patient Characteristics Asians NHPI Median age at diagnosis, years (range) 52 (33-74) 63 (46-78) Median BMI (range) 25.4 (18.8-39.6) 28.6 (23.8-50.6) Median sTILs % (range) 55 (20-80) 35 (5-90) Pathologic complete response (%) 30% 71%* *Out of 7 samples.