# Prognostic Significance of DNA Repair Gene mRNA Expression in Early-Stage Breast Cancer: Insights into Clinical Relevance

## TL;DR

This study shows that the mRNA levels of ATM, BLM, and WRN genes can predict survival outcomes in early-stage breast cancer patients.

## Contribution

The study identifies ATM, BLM, and WRN as prognostic markers for metastasis-free survival in early-stage breast cancer.

## Key findings

- High ATM mRNA expression is linked to longer metastasis-free survival in early-stage breast cancer.
- Low BLM mRNA expression correlates with better outcomes, especially in triple-negative breast cancer.
- High WRN mRNA expression is associated with significantly longer metastasis-free survival.

## Abstract

The prognostic and therapeutic roles of biological markers in early-stage breast cancer (eBC) warrant further investigation. Non-Breast Cancer (BRCA) genes, along with moderate- and low-penetrance breast cancer risk variant genes, are crucial for maintaining genome stability, yet their prognostic significance in eBC remains unclear. This study aimed to evaluate the impact of non-BRCA genes on clinical outcomes in eBC patients. Significant correlations were observed between the messenger ribonucleic acid (mRNA) expression levels of the genes Ataxia-telangiectasia mutated (ATM), Bloom helicase gene (BLM), and WRN RecQ Like Helicase (WRN) and patient prognosis. High mRNA expression of ATM was associated with longer metastasis-free survival (MFS). Conversely, lower mRNA expression of BLM correlated with favorable outcomes, particularly in triple-negative tumors. Additionally, high levels of WRN mRNA expression were linked to significantly longer MFS compared to low expression levels. This study highlights the prognostic significance of ATM, BLM, and WRN in predicting survival outcomes in eBC patients.

The prognostic significance of various biological and non-BRCA genetic in early-stage breast cancer (eBC) remains unclear and warrants further investigation. This study therefore aimed to evaluate the prognostic impact of these genes on clinical outcomes in breast cancer.

Patients included in this study were subdivided into two groups based on low and high messenger ribonucleic acid (mRNA) expression levels. Statistical analysis, including Kaplan-Meier curves, univariable, and multivariable Cox regression analyses, was performed to assess metastasis-free survival (MFS) of mRNA expression of non-BRCA genes. Subgroup analyses were also conducted among four different molecular subtypes of eBC.

Our analysis revealed significant correlations between mRNA-expression levels of Ataxia-telangiectasia mutated (ATM), Bloom helicase gene (BLM), and WRN RecQ Like Helicase (WRN) and patient prognosis. High mRNA expression of ATM correlated with longer MFS in the entire cohort (p = 0.022, Log Rank), and in luminal-B-like tumors (p = 0.036). Lower mRNA expression of BLM was associated with favorable outcomes (p = 0.011, Log Rank), particularly in triple-negative eBC (p = 0.030, Log Rank). Finally, high levels of WRN mRNA expression correlated with significantly longer MFS compared to low mRNA expression levels (p = 0.009, Log Rank).

This study underscores the prognostic significance of moderate penetrance breast cancer risk variant genes, such as ATM, BLM, and WRN, for survival outcomes in eBC.