Abstract C063: Associations of leptin and leptin receptor protein and gene expression with breast cancer clinicopathologic features

Abstract The adipokine, leptin (LEP) and its receptor (leptin receptor, LEPR), are hypothesized to play a role in breast cancer (BrCa) outcomes disparities. The objective of this study was to address the gaps in knowledge regarding the epidemiologic associations of LEP and LEPR protein and gene expression with breast cancer clinicopathologic features (namely, estrogen receptor [ER] status, and tumor grade, stage, size, and subtype). In the Women's Circle of Health Study, we used immunohistochemistry to assess protein expression in breast tumor tissue microarrays among a sample of 711 early stage BrCa cases. LEP and LEPR protein expression was scored semiquantitatively by a board-certified pathologist and we used NanoString digital, multiplexed assays to quantitatively assess gene expression of these biomarkers. Multivariable-adjusted logistic regression models were used to examine the associations of interest. Compared to ER+, LEP protein expression was lower (OR 0.54, 95% CI 0.30, 1.00), and LEPR protein (OR 3.95, 95% CI 2.02, 7.71) and gene expression (OR 1.003, 95% CI 1.001, 1.005) were higher among ER- BrCa cases. Compared to well/moderately differentiated tumors, LEPR protein (OR 2.46, 95% CI 1.40, 4.31) and gene expression (OR 1.002, 95% CI 1.000, 1.003) were higher among poorly differentiated tumors. Compared to luminal A, LEP protein expression was higher among non-luminal HER2-expressing (OR 3.34, 95% CI 1.20, 9.32) and TNBC subtypes (OR 2.02, 95% CI 1.00, 4.08), LEPR protein expression was lower among non-luminal HER2-expressing (OR 0.39, 95% CI 0.16, 0.94) and TNBC (OR 0.28, 95% CI 0.13, 0.57), and LEPR gene expression was lower in TNBC (OR 0.997, 95% CI 0.995, 0.999). LEP gene expression and LEPR protein and gene expression were inversely associated with tumor size (P-values <0.05). No major associations were observed between LEP and LEPR expression profiles and tumor stage. These findings suggest that LEP and LEPR protein and gene expression in the breast tumor microenvironment may serve as biomarkers contributing to interindividual differences in BrCa prognostic indicators and are important for understanding tumor heterogeneity and outcomes disparities. Funding: This study was supported by grants from the National Cancer Institute (K01CA193527, P01CA151135, R01CA100598, R01CA185623). Tumor samples were received, processed and tracked under the auspices of the Roswell Park Comprehensive Cancer Center DataBank and BioRepository Shared Resource, supported by P30CA16056 with support from the Breast Cancer Research Foundation to CBA. This work was also supported by the Biomedical Informatics and the Biospecimen Repository and Histopathology Service shared resources of Rutgers Cancer Institute of New Jersey, supported by P30CA072720. Citation Format: Adana A.M. Llanos, Baichen Xu, Bo Qin, Wenjin Chen, Marina A. Chekmareva, Lei Cong, Chi-Chen Hong, Song Yao, Christine B. Ambrosone, Elisa V. Bandera, Kitaw Demissie. Associations of leptin and leptin receptor protein and gene expression with breast cancer clinicopathologic features [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C063.