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Identification of the genetic-molecular profile of Breast Cancer with metastasis to the brain associated with a tumor progression model

Grant number: 20/07773-9
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2021
Effective date (End): July 31, 2024
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Márcia Maria Chiquitelli Marques Silveira
Grantee:Muriele Bertagna Varuzza
Home Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

Breast neoplasms are the main cause of cancer mortality among women, corresponding to 25% of new cases each year. When diagnosed at an early stage, it has an overall five-year survival rate of up to 90%. However, in more advanced stages, survival is reduced to about 24%, with 90% of women in stage IV, dying as a result of complications related to metastases. A common site of metastases from this neoplasm is the brain and the average life span after its onset, without a therapeutic approach, is 4 weeks. When treatment options are available, only 20% of patients survive more than 1 year. Considering that the brain is an unfavorable prognostic site, and the identification of the genetic-molecular profile in the primary tumor and in the metastatic site is a subject poorly described in the literature, we understand that to characterize the mutational and gene expression profile of the tumor microenvironment (tumor and immuno-oncological cells) of breast cancer with metastasis to the brain, it is extremely necessary. Our hypothesis is that the primary tumor has a specific mutational pattern and gene expression, distinct from brain metastasis, which may be associated with the evolution of metastatic clones. The present study aims to identify the genetic-molecular profile of samples of the primary tumor and metastasis to the brain. As brain metastasis is clinically aggressive, the identification of this genetic profile may contribute to the elucidation of the genetic-molecular mechanisms associated with a model of tumor progression of breast cancer with brain metastasis, and may be the target of relevant clinical application in the future, whether in the screening patients or elucidating a new therapeutic target.

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