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

Autor: Schettini, Francesco, Sobhani, Navid, Ianza, Anna, Triulzi, Tiziana, Molteni, Alfredo, Lazzari, Maria Chiara, Strina, Carla, Milani, Manuela, Corona, Silvia Paola, Sirico, Marianna, Bernocchi, Ottavia, Giudici, Fabiola, Cappelletti, Maria Rosaria, Ciruelos, Eva, Jerusalem, Guy, Loi, Sherine, Fox, Stephen B., Generali, Daniele
Zdroj: Breast Cancer Research & Treatment; Nov2020, Vol. 184 Issue 2, p421-431, 11p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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