Schettini, FrancescoSobhani, NavidIanza, AnnaTriulzi, TizianaMolteni, AlfredoLazzari, Maria ChiaraStrina, CarlaMilani, ManuelaCorona, Silvia PaolaSirico, MariannaBernocchi, OttaviaGiudici, FabiolaCappelletti, Maria RosariaCiruelos, EvaJerusalem, GuyLoi, SherineFox, Stephen BGenerali, Daniele2025-01-072025-01-072020-08-07https://hdl.handle.net/10668/25332mTOR inhibitor everolimus is used for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (mBC). No reliable predictive biomarker of response is available. Following evidences from other solid tumors, we aimed to assess the association between treatment-associated immune system features and everolimus activity. We retrospectively explored a correlation with the therapeutic activity of everolimus and tumor-associated immune pathways with ingenuity pathway analysis (IPA), neutrophil-to-lymphocyte ratio (NLR), circulating lymphocytes, and endothelial cells (CECs) in 3 different HR+ mBC studies, including the BALLET phase IIIb study. The circulating levels of CD3+/CD8+, CD3+/CD4+, and overall T lymphocytes were higher in responders versus non-responders at baseline (p = 0.017, p  4.4) (p = 0.01). IPA showed that the majority of immunity-related genes were found upregulated in responders compared to non-responders before treatment, but not after. Lymphocytes subpopulations, CECs and NLR could be interesting biomarkers predictive of response to everolimus-based regimens, potentially useful in daily clinical practice to select/monitor everolimus-based treatment in mBC. Further studies to confirm such hypotheses are warranted.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/BiomarkerBreast cancerEverolimusHormone receptorsImmunomodulationmTORAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsEndothelial CellsEverolimusFemaleHormonesHumansImmune SystemReceptor, ErbB-2Retrospective Studiesresearch article32770287open access10.1007/s10549-020-05856-31573-7217PMC7599144https://link.springer.com/content/pdf/10.1007/s10549-020-05856-3.pdfhttps://pmc.ncbi.nlm.nih.gov/articles/PMC7599144/pdf