Role of ATM as a prognostic biomarker in breast cancer: A systematic review and meta-analysis.

Abstract

e12705 Background: Breast cancer is the most common malignancy among women worldwide and remains a leading cause of cancer related mortality. Prognostic biomarkers are essential for risk stratification and personalized treatment. The ataxia-telangiectasia mutated (ATM) gene is a key regulator of the DNA damage response, and its altered expression has been linked to tumor progression and therapeutic resistance. However, the prognostic significance of ATM expression in breast cancer remains inconsistent. This study aimed to evaluate the prognostic role of ATM expression in breast cancer through a systematic review and meta analysis. Methods: This systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines and prospectively registered on PROSPERO. PubMed, Scopus, Web of Science, Embase, and the Cochrane Library were searched from inception to July 2025 for cohort studies assessing the association between ATM expression and breast cancer prognosis. Eligible studies reported hazard ratios (HRs) with 95% confidence intervals (CIs). Study quality was assessed using the modified Newcastle Ottawa Scale. Pooled HRs for disease free survival (DFS), breast cancer specific survival (BCSS), and disease-specific survival (DSS) were calculated using a random effects model. Results: Five cohort studies met the inclusion criteria and were included in the quantitative synthesis. Low ATM expression was significantly associated with poorer disease free survival (HR 1.69; 95% CI, 1.12–2.22; p = 0.01; I² = 0%) and breast cancer specific survival (HR 1.51; 95% CI, 1.03–2.20; p = 0.04; I² = 53%). No statistically significant association was observed between ATM expression and disease specific survival (HR 3.13; 95% CI, 0.77–12.77; p = 0.11), with substantial heterogeneity (I² = 79%). Conclusions: Low ATM expression is associated with adverse prognostic outcomes in breast cancer, particularly reduced disease free and breast cancer specific survival. ATM may represent a clinically relevant prognostic biomarker; however, further large scale prospective studies are required to validate its prognostic utility and guide biomarker driven therapeutic strategies.