Abstract Background: Aberrant activation of the mammalian Target of Rapamycin (mTOR) pathway is implicated in breast carcinogenesis and outcomes. Based on protein expression data, the activation could be heterogeneous by race, body fatness, and tumor clinicopathological characteristics. To understand potential impacts of mTOR pathway signaling in breast cancer, we evaluated the association of race and clinicopathological characteristics with gene expression of select mTOR pathway genes in breast tumors. Methods: Study participants were from the Women's Circle of Health Study (WCHS), complemented with samples from the Roswell Park Pathology Network Shared Resource (PNSR). Tumor tissue blocks were collected from 367 newly-diagnosed breast cancer cases (190 Black and 177 White women). Gene expressions of AKT1, EIF4EBP1, MTOR, RPS6KB2, TSC1 were quantitated using NanoString assays. Generalized linear models were performed to relate gene expression levels with demographic and clinicopathological variables. The regression coefficient (β) was converted to percentage difference. Additionally, we conducted an external validation of mTOR gene expression using data from The Cancer Genome Atlas (TCGA; N=332). Results: Study participants were mostly within the ages of 51 to 65 years old. Black women had lower expression levels of AKT1, MTOR, RPS6KB2 and TSC1 compared to White women. Black race vs White race was significantly associated with lower gene expression of AKT1 (-21.34%, 95% CI = -31.61%, -8.61%) and RPS6KB2 (-12.19%, 95% CI = -19.75%, -3.92%). The racial differences in expression levels of these two genes were consistent across luminal A, luminal B, HER2-enriched, and triple-negative subtypes. Higher tumor grade was associated with higher expression levels of EIF4EBP1 and RPS6KB2, but with lower expression of TSC1. In comparison to luminal A tumors, luminal B tumors had higher expression of RPS6KB2 (17.35%, 95% CI = 4.08%, 32.31%); whereas HER2-enriched (-23.66%, 95% CI= -41.73%, -1.00%) and triple-negative (-22.89%, 95% CI= -40.55%, -1.00%) had lower expression of TSC1. All these associations were unchanged after additionally adjusting for body mass index in a subset. Similarly, results from the TCGA data showed that in comparison to luminal A tumors, luminal B tumors had higher expression of RPS6KB2 (53.73%, 95% CI = 27.12%, 87.76%) whereas HER2-enriched had a lower expression of TSC1 (-26.66%, 95% CI = -43.45%, -4.88%) and triple-negative subtype had a lower expression of TSC1 (-17.30%, 95% CI = -50.68%, -3.05%). Conclusions: Variables such as race and breast cancer subtypes should be considered in studying the mTOR pathway genes in breast cancer tumors. Citation Format: Mmadili N. Ilozumba, Song Yao, Adana A. Llanos, Angela Omilian, Weizhou Zhang, Susmita Datta, Chi-Chen Hong, Warren Davis, Thaer Khoury, Christine B. Ambrosone, Ting-Yuan D. Cheng. Breast tumor gene expression in the mTOR pathway and clinicopathological characteristics in Black women and White women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 869.