Immune system and angiogenesis-related potential surrogate biomarkers of response to everolimus-based treatment in hormone receptor-positive breast cancer: an exploratory study.

Francesco Schettini, Navid Sobhani, Anna Ianza, Tiziana Triulzi, Alfredo Molteni, Maria Chiara Lazzari, Carla Strina, Manuela Milani, Silvia Paola Corona, Marianna Sirico, Ottavia Bernocchi, Fabiola Giudici, Maria Rosaria Cappelletti, Eva Ciruelos, Guy Jerusalem, Sherine Loi, Stephen B. Fox, Daniele Generali

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: mTOR 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. METHODS: 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. RESULTS: 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 textless 0.001, p = 0.034) and after treatment (p = 0.01, p = 0.003, p = 0.023). Reduced CECs, a tumor neoangiogenesis marker, were observed in responders after treatment (p textless 0.001). Patients with low NLR (≤ 4.4) showed a better progression-free survival compared to patients with high NLR (textgreater 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. CONCLUSIONS: 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.
Original languageEnglish
JournalBreast Cancer Research and Treatment
Issue number2
Publication statusPublished - Nov 1 2020

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