Abstract P6-15-12: A functional approach to the molecular basis of neoadjuvant treatment response in breast cancer

Abstract

Abstract BACKGROUND Breast cancer is a diverse and heterogeneous disease. The use of neoadjuvant treatments has improved the prognosis of localized breast cancer. However, molecular basis of neoadjuvant treatment response and resistance remains unknown. Clinical data has uncovered the existence of different tumor responses to neoadjudvant chemotherapy, allowing the classification of patients in different groups. Gene expression profile description of the different patient groups provide essential information in the clinical decision making as well as to allow a deeper knowledge of this disease. MATERIALS AND METHODS A breast cancer tumor dataset was obtained from the Gene Expression Omnibus (GSE41998) and from a phase II trial (NCT00455533). 279 tumors from previously untreated women with primary invasive breast adenocarcinoma were included in this study. Whole genome gene expression profiling was performed using Affymetrix GeneChip gene expression microarrays.Differentially expressed genes were chosen selecting 3000 more variable probes among all patients and were used to construct four networks of gene functional interactions, one for all tumors and three for each molecular subtype independently. Functional structure was performed using probabilistic graphical models with local minimum Bayesian Information Criterion. Data analyses were carried out using MeV, BRB Array Tools, R, Cytoscape software suites and DAVID web tools. RESULTS Regardless of tumor molecular subtype, tumors showing a complete response to treatment showed higher "Immune response (MHCII)", "Immune response (chemotaxis)", "Immune response (B cell)“ and "Immune response (Interferon)” nodes activities compared to resistant tumors (stable disease tumors). These differences are also observed when analyzing tumor molecular subgroups (Luminal A, Luminal B and Basal-like) separately. Moreover, complete response tumors, showed significantly higher levels of lymphocytic cell lineage markers (CD4, CD8 and CD20). CONCLUSION This type of approach allows seeing differences at biological process levels rather than at the individual gene level.Tumors that respond to neoadjuvant treatment showed higher “Immune” nodes activity than resistant tumors and these differences were also showed in analyses stratified by molecular subtype. Besides, complete response tumors presented higher values of lymphocyte cell lineage markers which might suggest a greater amount of tumor-infiltrating lymphocytes (TILs). These results can suggest that patients' immune system could play an important role in the response to neoadjuvant chemotherapy treatment. Citation Format: Zamora Auñón P, Zapater-Moros A, Trilla-Fuertes L, Gamez-Pozo A, Prado-Vázquez G, Llorente-Armijo S, Lopez-Vacas R, Main P, Espinosa Arranz E, Fresno-Vara JA. A functional approach to the molecular basis of neoadjuvant treatment response in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-12.