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Breast of you : inter-tumour heterogeneity of breast cancer and it’s follow-up through ctDNA sequencing
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Resumo(s)
O cancro da mama é tipo de cancro mais prevalente em mulheres no mundo e apesar dos avanços na deteção, prevenção e tratamento mantém-se responsável por causar mais de 650 mil mortes por ano.
O cancro de mama representa uma doença heterogénea com diferentes características biológicas e apresentações clínicas que guiam a gestão da doença e na abordagem terapêutica.
As biópsias líquidas são vistas atualmente como uma nova estratégia na gestão das doentes de cancro de mama com a análise de ctDNA a apresentar resultados promissores na deteção precoce de tumores da mama e na monitorização da progressão da doença.
A análise das biópsias líquidas é baseada em técnicas de PCR e de next-generation sequencing (NGS) que podem ser aplicadas na monitorização de mutações durante o tratamento, na descoberta de novas alterações genéticas subjacentes à resistência à terapêutica, na identificação de novos alvos de terapêutica dirigida e na caracterização das cargas mutacionais para guiar potencial imunoterapia.
De forma a investigar ctDNA como marcador diagnóstico e preditivo de resposta terapêutica, analisámos uma cohort retrospetiva e preditivo de resposta terapêutica, analisámos uma cohort retrospetiva de amostras correspondentes de biópsia tecidual e de ctDNA no sangue utilizando um painel de sequenciação baseado em técnicas de NSG. Ao sequenciar 40 tecidos tumorais de uma região de 40 pacientes com o diagnóstico de cancro de mama metastático, sem tratamento prévio, tentámos investigar o status de heterogeneidade inter-tumoral. Para além disso, foi realizada a comparação das mutações genéticas detetadas nas biópsias sólidas e correspondente ctDNA, por forma a avaliar a carga da doença e alterações genéticas ao longo do tratamento paliativo. Com este estudo tentámos criar evidência para a utilização da sequenciação de ctDNA de amostras de sangue no diagnóstico e follow-up de doentes de cancro de mama
Breast cancer is the most prevalent cancer in women worldwide, and although all the improvements in detection, prevention and treatment is still responsible for causing more than 650 thousand deaths per year. Breast cancer represents a heterogeneous disease with different biological characteristics and clinical behaviours which guide the management of the disease and therapeutic approach. Liquid biopsy is now seen as a new strategy on the management of breast cancer patients with ctDNA analysis showing promising results in the early detection of breast tumours and monitoring of progression. Analysis of liquid biopsies are PCR-based techniques and next-generation sequencing (NGS) that can be used for monitoring mutations during treatment, for the discovery of genetic changes underlying therapy resistance, for identifying new actionable targets, and for characterizing mutational loads to guide potential immunotherapy. To investigate further possible ctDNA markers of diagnostic and predictive of response, we analyzed a retrospective cohort of match tissue and blood ctDNA samples using NGS-based panel sequencing techniques. By sequencing 40 single-region tumour tissue from 40 metastatic breast cancer patients, with no prior treatment, we aimed to investigate the status of inter-tumoral heterogeneity in his population. Moreover, further comparison of gene mutation detectable in solid biopsies and matched ctDNA, unabled the study of disease burden and responses over the course of palliative treatment. With this study, we aim to provide evidence for the utility of blood ctDNA sequencing in the diagnosis and follow-up of breast cancer patients.
Breast cancer is the most prevalent cancer in women worldwide, and although all the improvements in detection, prevention and treatment is still responsible for causing more than 650 thousand deaths per year. Breast cancer represents a heterogeneous disease with different biological characteristics and clinical behaviours which guide the management of the disease and therapeutic approach. Liquid biopsy is now seen as a new strategy on the management of breast cancer patients with ctDNA analysis showing promising results in the early detection of breast tumours and monitoring of progression. Analysis of liquid biopsies are PCR-based techniques and next-generation sequencing (NGS) that can be used for monitoring mutations during treatment, for the discovery of genetic changes underlying therapy resistance, for identifying new actionable targets, and for characterizing mutational loads to guide potential immunotherapy. To investigate further possible ctDNA markers of diagnostic and predictive of response, we analyzed a retrospective cohort of match tissue and blood ctDNA samples using NGS-based panel sequencing techniques. By sequencing 40 single-region tumour tissue from 40 metastatic breast cancer patients, with no prior treatment, we aimed to investigate the status of inter-tumoral heterogeneity in his population. Moreover, further comparison of gene mutation detectable in solid biopsies and matched ctDNA, unabled the study of disease burden and responses over the course of palliative treatment. With this study, we aim to provide evidence for the utility of blood ctDNA sequencing in the diagnosis and follow-up of breast cancer patients.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2022
Palavras-chave
Biópsia líquida Neoplasias da mama Sequenciamento de nova geração Análise ctDNA Oncologia