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 Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2021
• End date: August 02, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Márcia Maria Chiquitelli Marques Silveira
• Grantee: Muriele Bertagna Varuzza
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Associated scholarship(s): 22/11820-8 - Tumor subclonal reconstruction in breast cancer with brain metastasis, BE.EP.DR

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. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VARUZZA, MURIELE BERTAGNA; WINATA, HELENA; PATEL, YASH; MOOTOR, MOHAMMED FAIZAL EEMAN; SOUZA, CRISTIANO DE PADUA; BOUTROS, PAUL CHRISTOPHER; CHIQUITELLI MARQUES SILVEIRA, MARCIA MARIA. Subclonal mutational signatures in breast cancer brain metastases.. Journal of Clinical Oncology, v. 42, n. 16, p. 1-pg., 2024-06-01. (20/07773-9)