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

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