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Open Access 01-11-2020 | Breast Cancer | Clinical trial

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

Authors: 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

Published in: Breast Cancer Research and Treatment | Issue 2/2020

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 < 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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Title: Immune system and angiogenesis-related potential surrogate biomarkers of response to everolimus-based treatment in hormone receptor-positive breast cancer: an exploratory study
Authors: 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
Publication date: 01-11-2020
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Everolimus
Biomarkers
Published in: Breast Cancer Research and Treatment / Issue 2/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05856-3

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