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

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.