TY - JOUR
T1 - Immune system and angiogenesis-related potential surrogate biomarkers of response to everolimus-based treatment in hormone receptor-positive breast cancer: an exploratory study.
AU - Schettini, Francesco
AU - Sobhani, Navid
AU - Ianza, Anna
AU - Triulzi, Tiziana
AU - Molteni, Alfredo
AU - Lazzari, Maria Chiara
AU - Strina, Carla
AU - Milani, Manuela
AU - Corona, Silvia Paola
AU - Sirico, Marianna
AU - Bernocchi, Ottavia
AU - Giudici, Fabiola
AU - Cappelletti, Maria Rosaria
AU - Ciruelos, Eva
AU - Jerusalem, Guy
AU - Loi, Sherine
AU - Fox, Stephen B.
AU - Generali, Daniele
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
M3 - Article
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
SN - 0167-6806
IS - 2
ER -