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

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Schettini, F; Sobhani, N; Ianza, A; Triulzi, T; Molteni, A; Lazzari, MC; Strina, C; Milani, M; Corona, SP; Sirico, M; ...Date
2020-08-07Source Title
Breast Cancer Research and TreatmentPublisher
SPRINGERAffiliation
Sir Peter MacCallum Department of OncologyMetadata
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Schettini, F., Sobhani, N., Ianza, A., Triulzi, T., Molteni, A., Lazzari, M. C., Strina, C., Milani, M., Corona, S. P., Sirico, M., Bernocchi, O., Giudici, F., Cappelletti, M. R., Ciruelos, E., Jerusalem, G., Loi, S., Fox, S. B. & Generali, D. (2020). Immune system and angiogenesis-related potential surrogate biomarkers of response to everolimus-based treatment in hormone receptor-positive breast cancer: an exploratory study. BREAST CANCER RESEARCH AND TREATMENT, 184 (2), pp.421-431. https://doi.org/10.1007/s10549-020-05856-3.Access Status
Open AccessAbstract
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 < 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 < 0.001). Patients with low NLR (≤ 4.4) showed a better progression-free survival compared to patients with high NLR (> 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.
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