Probabilistic graphical models relate immune status with response to neoadjuvant chemotherapy in breast cancer.

Andrea Zapater-Moros,Hilario Navarro,Guillermo Prado-Vázquez,Jorge M Arevalillo,Mariana Díaz-Almirón,Juan Ángel Fresno Vara,Lucía Trilla-Fuertes,Paloma Maín,Angelo Gámez-Pozo,Enrique Espinosa,Pilar Zamora,Jaime Feliú

doi:10.18632/oncotarget.25496

Abstract

Breast cancer is the most frequent tumor in women and its incidence is increasing. Neoadjuvant chemotherapy has become standard of care as a complement to surgery in locally advanced or poor-prognosis early stage disease. The achievement of a complete response to neoadjuvant chemotherapy correlates with prognosis but it is not possible to predict who will obtain an excellent response. The molecular analysis of the tumor offers a unique opportunity to unveil predictive factors. In this work, gene expression profiling in 279 tumor samples from patients receiving neoadjuvant chemotherapy was performed and probabilistic graphical models were used. This approach enables addressing biological and clinical questions from a Systems Biology perspective, allowing to deal with large gene expression data and their interactions. Tumors presenting complete response to neoadjuvant chemotherapy had a higher activity of immune related functions compared to resistant tumors. Similarly, samples from complete responders presented higher expression of lymphocyte cell lineage markers, immune-activating and immune-suppressive markers, which may correlate with tumor infiltration by lymphocytes (TILs). These results suggest that the patient’s immune system plays a key role in tumor response to neoadjuvant treatment. However, future studies with larger cohorts are necessary to validate these hypotheses.

Highlights

Breast cancer is the most common neoplasm and the fifth cause of cancer-associated death among women [1]
Luminal A disease, which accounts for 67% of all tumors, shows high expression of genes related to hormone receptors and low expression of genes related to cell proliferation
A gene expression-based probabilistic graphical model analysis of breast cancer showed that www.oncotarget.com immune functional nodes were related to pathological response to neoadjuvant chemotherapy

Summary

Introduction

Breast cancer is the most common neoplasm and the fifth cause of cancer-associated death among women [1]. Provide a system of classification and clinical diagnosis. Seventy percent of the tumors are hormonal receptor positive, and HER2 overexpression is observed in 15% of cases. ER, PR and HER2 are known as Triple Negative Breast Cancer (TNBC) and do not respond to the aforementioned therapies. A molecular classification of breast cancer defined four intrinsic subtypes [4]. Luminal A disease, which accounts for 67% of all tumors, shows high expression of genes related to hormone receptors and low expression of genes related to cell proliferation. Luminal B, HER2enriched and Basal-like subtypes have a more aggressive phenotype [5] [6, 7]

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