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Updated: Jun 14, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Custom target-sequencing in triple-negative and luminal breast cancer from young Brazilian patients
Pedro Adolpho de Menezes Pacheco Serio1, Daniela Marques Saccaro1, Ana Carolina Ribeiro Chaves de Gouvêa2
1Comprehensive Center for Precision Oncology (C2PO), Centro de Investigação Translacional em Oncologia (CTO), Departamento de Radiologia e Oncologia, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.
Objectives:
To identify somatic mutations in tumors from young women with triple-negative or luminal breast cancer, through targeted sequencing and to explore the cancer driver potential of these gene variants.
Methods:
A customized gene panel was assembled based on data from previous sequencing studies of breast cancer from young women. Triple-negative and luminal tumors and paired blood samples from young breast cancer patients were sequenced, and identified gene variants were searched for their driver potential, in databases and literature. Additionally, the authors performed an exploratory analysis using large, curated databases to evaluate the frequency of somatic mutations in this gene panel in tumors stratified by age groups (every 10 years).
Results:
A total of 28 young women had their tumoral tissue and blood samples sequenced. Using a customized panel of 64 genes, the authors could detect cancer drivers in 11/12 (91.7 %) TNBC samples and 11/16 (68.7 %) luminal samples. Among TNBC patients, the most frequent cancer driver was TP53, followed by NF1, NOTCH1 and PTPN13. In luminal samples, PIK3CA and GATA3 were the main cancer drivers, and other drivers were GRHL2 and SMURF2. CACNA1E was involved in both TN and luminal BC. The exploratory analysis also indicated a role for SMURF2 in luminal BC development in young patients.
Conclusions:
The data further indicates that some cancer drivers are more common in a specific breast cancer subtype from young patients, such as TP53 in TNBC and PIK3CA and GATA3 in luminal samples. These results also provide additional evidence that some genes not considered classical cancer-causing genes, such as CACNA1E, GRHL2 and SMURF2 might be cancer drivers in this age group.
Insights
This study identified key cancer drivers in young women with triple-negative breast cancer (TNBC) and luminal breast cancer (BC). TP53 was frequent in TNBC, while PIK3CA and GATA3 were common in luminal BC, with novel drivers also noted.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) and luminal breast cancer (BC) disproportionately affect young women.
- Understanding the genetic drivers of these cancers in younger populations is crucial for targeted therapies.
Purpose of the Study:
- To identify somatic mutations and explore cancer driver potential in tumors from young women with TNBC and luminal BC.
- To investigate the frequency of specific gene mutations across different age groups.
Main Methods:
- Targeted sequencing of a 64-gene panel in tumor and blood samples from 28 young breast cancer patients.
- Bioinformatic analysis to identify somatic mutations and assess their driver potential using databases and literature.
- Exploratory analysis of mutation frequency stratified by age.
Main Results:
- Cancer drivers were detected in 91.7% of TNBC and 68.7% of luminal BC samples.
- TP53 was the most frequent driver in TNBC; PIK3CA and GATA3 were predominant in luminal BC.
- CACNA1E, GRHL2, and SMURF2 were identified as potential drivers, with SMURF2 implicated in luminal BC in young patients.
Conclusions:
- Specific cancer drivers are associated with breast cancer subtypes in young patients (e.g., TP53 in TNBC, PIK3CA/GATA3 in luminal BC).
- Genes like CACNA1E, GRHL2, and SMURF2 may act as novel cancer drivers in this demographic, warranting further investigation.
