Background: Olaparib (AZD2281, KU-0059436) is a poly ADP ribose polymerase (PARP) inhibitor. Biomarkers that predict a response to olaparib in EC are not fully established. The aim of this study is to identify pharmacodynamic and pharmacogenetic biomarkers associated with a short term exposure to olaparib in type I primary EC surgical patients (pts). Methods: In this phase 0, multicenter, single arm, window of opportunity trial, women diagnosed with type I primary EC received olaparib tablets (oral 300mg/BID; 4 weeks) before surgery. Biological effects were evaluated by comparing the initial biopsy and the tumor tissue at surgery. The primary endpoints were the significant inhibition of cyclin D1, Ki67 and active caspase 3 activity. Secondary objectives included the correlation between PARP inhibition and cell proliferation, angiogenesis and tumor-tissue biomarkers. The predictive role of PTEN, PMS2 and MSH6 mutations were evaluated. We control multiple testing issues with a false discovery rate (FDR) of 10%. Results: From March 2016, 41 pts have been screened, 36 included, 23 treated and 19 could be studied in biomarker analysis. Median age was 63y (51-82); 100% were endometrioid and clinical stage was I (17, 89.5%) and stages II, III and IV (2, 10.5%). Median time of olaparib exposure was 21 days (13-32). Significant inhibition was declared for cyclin D1 (p = 0.01), but not for Ki67 and active caspase 3 immunostaining. Differences in PARP1 baseline and post-treatment immunostaining correlates (Rho > 0.45; p < 0.05) with differences in pre-post cyclin D1, Ki67, phospho-histone H3, p50, VEGF and HIF1α measures. However, only cyclin D1 (Rho = 0.771, p < 0.001) showed a significant correlation under FDR criterion. Genetic alterations did not show differences in pre-post treatment measures. The most common AEs were nauseas (31.6%), vomiting (21.1%) and fatigue (21.1%) grade 1 and 2. No surgery was delayed due to toxicity. Conclusions: The study has identified some potential biomarkers associated with olaparib exposure in cell proliferation/apoptosis pathways that might help select best candidates. Clinical trial information: NCT02506816