Introduction Endocrine therapy (ET) is a well-tolerated treatment strategy among women with low grade, hormone receptor positive advanced endometrial cancer (EC). Currently, we lack effective biomarkers to refine beyond ER status which patients will respond to treatment.

Methods Gene expression profiling was performed using the NanoString Breast Cancer 360 panel on RNAs extracted from macrodisssected formalin fixed paraffin embedded tissues from 12 patients who received ET for metastatic disease at the Sunnybrook Odette Cancer Centre between 2016-2018. In addition, proteomic profiling using NanoString’s GeoMx system was performed. A ≤ 6 months duration of first line ET was used to define endocrine resistance.

Results Median age was 62 (range 39-85); 6(50%) had grade 1, 3(25%) grade 2 and 3(25%) grade 3 tumors; 5 with known protein TP53 immunohistochemical status had wild type TP53. The majority (58%) had mismatch repair (MMR)-proficient disease. Median duration of 1^st ET was 6 months (range 2-50 months). Supervised hierarchical clustering identified differential gene expression in several genes related to DNA repair and cell cycle. Although trained for breast cancer, bespoke gene signatures for homologous recombination deficiency (HRD) and BRCAness were significant (unadjusted p-value ≤0.05) between groups. Most cancers showed low gene expression of immune markers. Proteomic profiling demonstrated increased expression of proteins associated with dendritic and T cells patients within the TME in patients with endocrine sensitive tumors.

Conclusion/Implications In this small retrospective cohort of patients, HRD and BRCAness gene signatures as well as expression of proteins associated with dendritic and T cells in the TME were associated with endocrine sensitivity.