Prognostic value of androgen receptor expression in triple-negative breast cancer: a systematic review and meta-analysis

Abstract

Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression, with limited therapeutic options. TNBC exhibits high tumor heterogeneity and a worse prognosis, including early metastasis, and high recurrence and mortality rates. In this context, the expression of androgen receptor (AR) has been suggested as a potential prognostic biomarker in TNBC. ARs are steroid-dependent transcription factors, able to modulate cell proliferation, apoptosis, and tumor invasion, and may be associated with overall survival and disease-free survival in TNBC. Objective: To investigate the prognostic value of AR in TNBC, as assessed by immunohistochemistry, through a systematic review and meta-analysis. Methods: A systematic review was conducted according to PRISMA 2020, with a protocol registered in PROSPERO (CRD420261347726). Data were obtained from the PubMed/MEDLINE database, including 14 studies from the last ten years. Kaplan–Meier curves were reconstructed using Guyot's algorithm. Random-effects meta-analysis with 95% confidence interval (CI) was used to assess the prevalence of AR positivity. Heterogeneity was analyzed using I², with a leave-one-out sensitivity analysis. Publication bias was assessed using funnel plots and Egger's test, and risk of bias was assessed using the Joanna Briggs Institute criteria, with analyses performed in R 4.5.2 software. Results: The 14 studies were included in the meta-analysis (n=1,922), and AR expression was positive in 36.6% of the cases (95%CI 29.99–43.20; I²=92.5%). Kaplan–Meier curves demonstrated worse disease-free survival (p=0.03) and overall survival (p<0.001) in AR+ TNBC patients. Sensitivity analyses confirmed the robustness of the findings, and Egger's test did not indicate publication bias (p=0.53). Conclusion: AR expression in TNBC was associated with worse overall and disease-free survival, reinforcing its role as a potential prognostic biomarker in risk stratification and possibly guiding individualized therapeutic strategies.