Identification of immuno-oncology biomarkers in advanced breast cancer and the role in brain metastasis

• Grant number: 18/19471-7
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2019
• End date: July 31, 2021
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Márcia Maria Chiquitelli Marques Silveira
• Grantee: Márcia Maria Chiquitelli Marques Silveira
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Associated researchers: Adriane Feijó Evangelista ; Cristiano de Pádua ; René Aloisio da Costa Vieira ; Rui Manuel Vieira Reis ; Vinícius Duval da Silva

Abstract

Breast cancer are the leading cause of cancer mortality among women, accounting for 25% of new cases each year. When diagnosed at an early stage, breast cancer has a five-year overall survival rate of up to 90%. In the more advanced stages of the disease, survival is reduced to about 24%, and 90% of women in stage IV due to complications related to metastasis. Breast cancer is the second major cause of brain metastasis, behind only lung cancer, with a mean duration of 4 weeks when there is of brain metastasis involvement without a therapeutic approach. Despite efforts the current treatment resources (radiotherapy or neurosurgery) only about 20% of patients survive with time greater than 1 year. Thus, the evaluation of genetic and molecular changes in both primary tumor and the metastatic site is very poorly described in the literature, with the majority of studies with only primary tumor approach. Considering especially that breast cancer brains metastasis is a very poor prognostic site, we conceive that characterizing mutational and gene expression profile of elements that make up the tumor microenvironment (tumor cells and immuno-oncology) at primary tumor versus brain metastasis, is extremely necessary. Our hypothesis is that the primary tumor has a specific genetic pattern (mutational and gene expression) different of brain metastases. This pattern may be associated with the evolution of metastatic clones from a breast cancer progression model. With clinically aggressive brain metastasis, the identification of this genetic pattern (mutation and gene expression) may be correlated with lower survival. The main objective of this study was to identify the mutational and gene expression profile in paired samples from primary breast tumor with metastasis to the CNS. The results of this project may contribute to the elucidation of genetic-molecular mechanisms associated with a model of clonal evolution of breast cancer with metastasis to the CNS. We conceive that such characterization may be the target of relevant clinical application in the future, or in the screening of patients with worse prognosis or in the possible elucidation of a therapeutic target. (AU)