Snædís Ragnarsdóttir, Linda Viðarsdóttir, Laufey Tryggvadóttir, Elínborg Ólafsdóttir and Stefán Sigurðsson
Introduction
Breast cancer (BC) patients with estrogen receptor-positive (ER+) tumors are known to have a favorable prognosis. However, a specific subgroup of these patients, particularly those carrying BRCA2 mutations, show poorer treatment outcomes. These patients are currently being treated as other ER+ BC patients but need more aggressive or targeted treatment. The goal of this study is to understand the aggressiveness of BRCA2 ER+ tumors and find suitable drug regimens for this subgroup of patients.
Methods and data
We aim to study the impact of BRCA2 mutations on the development and progression of BC with a focus on estrogen signaling, DNA damage and gene expression. We’ll look at how estrogen signaling affects DNA damage response in BRCA2-deficient cells. This will be done by identifying genes contributing to tumor invasiveness in BRCA2 ER+ tumors and analyzing how BRCA2-deficiency affects BC cells’ aggressiveness and metastatic behavior.
Results
BRCA2 ER+ tumors are more aggressive and more likely to develop distant metastasis, suggesting a worse disease progression. Differential expression analysis identified three genes, CELA1, HPSE2 and RSPH6A, linked to invasiveness and metastasis, as upregulated in BRCA2 ER+ tumors. These findings can be used to design targeted treatments to effectively treat these tumors
Conclusions
This study emphasizes the need for more targeted treatment regimens for BRCA2 ER+ BC, highlighting the importance of understanding the molecular drivers of aggressiveness and metastasis. Integrating transcriptomic analysis will help identify genes and pathways involved in the progression of BRCA2 ER+ BC, leading to the identification of potential therapeutic targets.
