Abstract PR008: Racial and Ethnic Differences in the Biological Signatures of Breast Tumors and the Immune-microenvironment: The Multiethnic Cohort Study
Authors: Loo Lenora WM , Li Yuquing , White Kami K. , Aparicio Jose A. , Setiawan Veronica W. , Haiman Christopher A. , Wu Anna H. , Wilkens Lynne R. , Le Marchand Loic , Hernandez Brenda Y. , Cheng Iona 
Published: September 2024

Abstract
Background: In the U.S., there are stark racial and ethnic differences in the incidence and mortality of breast cancer that cannot be fully explained by lifestyle and environmental factors. The contribution of tumor biology to these differences in breast cancer outcomes across race and ethnicity is poorly understood. We conducted a preliminary analysis of the racial and ethnic differences in the gene expression profiles of biological signatures of breast tumors within in the Multiethnic Cohort Study (MEC). Methods: For 279 postmenopausal females with invasive breast cancer within the MEC, we examined 42 breast cancer signatures based on gene expression profiling of formalin-fixed paraffin-embedded breast tumors using the NanoString nCounter Breast Cancer 360™ (BC360) Panel. This included 36 African American, 62 Japanese American, 51 Latino, 65 Native Hawaiian, and 65 White females. Multivariable linear regression was conducted to examine racial and ethnic differences in gene expression levels, adjusting for age at diagnosis, stage (localized or regional/distant), and hormone receptor status (HR- positive, negative, or unknown). A Bonferroni corrected p-value threshold of 0.0019 (p=0.05/42 tests) was used to determine statistical significance. Results: We identified racial and ethnic differences in breast tumor gene expression signatures for four broad categories of breast tumor biology: breast cancer-specific, tumor, immune, and tumor microenvironment. Specifically, the differentially expressed signatures in these four categories were: breast cancer-specific (CDK4 p&lt;0.001; ER-signaling p=0.013), tumor (apoptosis p=0.004; p53 p=0.002; proliferation p=0.026; cell adhesion p=0.029; SOX2 p=0.002), immune (B7-H3 p=0.024; CD8 T-cells p=0.037; MHC2 p=0.032) and tumor microenvironment (hypoxia p=0.022) signatures. Racial and ethnic differences in the expression levels of the cyclin-dependent kinase 4 (CDK4) signature was found to be statistically significant (p&lt;0.001). In comparison to White females, increased expression of the CDK4 signature was observed in breast tumors of African American (p=0.001) and Latino (p=0.001) females and no differences were observed for Japanese American and Native Hawaiian females. Conclusion: Our preliminary results suggest racial and ethnic differences in breast tumor biology and the immune-microenvironment. As CDK4 is a key regulator of cell cycle progression, the increased expression of CDK4 in breast tumors from African American and Latino females compared to White females may reflect greater proliferation activity. CDK4 is a drug target of CDK4/6 inhibitors that could potentially serve as a basis for population-guided treatment strategies. Future work will examine additional breast tumor samples and evaluate association with clinico-pathological characteristics and survival across this multiethnic population.
Citation Format: Lenora WM Loo, Yuquing Li, Kami K. White, Jose A. Aparicio, Veronica W. Setiawan, Christopher A. Haiman, Anna H. Wu, Lynne R. Wilkens, Loic Le Marchand, Brenda Y. Hernandez, Iona Cheng. Racial and Ethnic Differences in the Biological Signatures of Breast Tumors and the Immune-microenvironment: The Multiethnic Cohort Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr PR008.