Prognostic Significance of Androgen Receptor Expression in Triple Negative Breast Cancer: A Systematic Review and Meta-Analysis

Abstract

The androgen receptor (AR) is increasingly considered as a potential biomarker for breast cancer. Nevertheless, the prognostic value of AR expression in patients with triple negative breast cancer (TNBC) remains controversial. Therefore, in this meta-analysis, we investigated AR expression and its impact on survival outcome. PubMed, Embase, the Cochrane Library, and references of articles were searched to identify relevant studies that investigated the association between AR expression and prognosis in patients diagnosed with TNBC and were published between 1946 and May 2019. The hazard ratio (HR) and confidence interval (CI) of disease-free survival, overall survival, distant disease-free survival, and recurrence-free survival were weighted and pooled by using the fixed-effect or randomeffect model based on the heterogeneity of included studies. A total of 27 studies including 4914 patients with TNBC were included. AR was expressed in 27.96% (1315/4703) of patients with TNBC. In addition, AR expression in TNBC was not associated with disease-free survival (HR, 0.923; 95% CI, 0.671-1.271; P ¼ .634), overall survival (HR, 0.910; 95% CI, 0.678-1.222; P ¼ .531), distant disease-free survival (HR, 1.02; 95% CI, 0.96-1.08; P ¼ .489), or recurrence-free survival (HR, 0.957; 95% CI, 0.462-1.982; P ¼ .906) in TNBC, regardless of confounding factors and heterogeneity that existed among included studies. In patients with TNBC, AR expression is not associated with prognosis.

Practical classification of triple-negative breast cancer: intratumoral heterogeneity, mechanisms of drug resistance, and novel therapies

“…Representing 10–15% of all TNBCs, androgen receptor (AR)-positive tumors are characterized by low proliferation rates and luminal-like gene expression profile, being inherently resistant to chemotherapy 20 – 23 , 34 , 49 . By contrast, AR expression assessed by IHC does not seem to imply a worse prognosis 50 . AR is a ligand-activated transcription factor that exerts genomic and non-genomic effects on cells by involving different intracellular signaling pathways and promoting tumor proliferation and invasiveness 51 , 52 .…”

Androgen Receptor in Breast Cancer: From Bench to Bedside

“…However, in a meta-analysis of 27 studies, including 4,914 TNBC patients, AR expression was not related to DFS, OS, distant DFS, or recurrence-free survival ( 52 ). Moreover, a recent study about peculiar clinical groups, including TNBC patients treated with or without radiation, showed a noticeable correlation between AR expression and locoregional recurrence only in patients who had radiation therapy, suggesting that AR expression might be a marker predicting the response to radiotherapy in TNBC ( 53 ).…”

Brain Metastases from Ovarian Cancer: Current Evidence in Diagnosis, Treatment, and Prognosis

“…A recent meta-analysis [52] suggested that ER negativity was an independent risk factor for BMs development, and that the triple-negative (ER, PgR and HER-2 negative) breast cancers showed shorter time to BMs development from the diagnosis of the primary tumor, compared to other breast cancer subtypes. Few data are available concerning AR expression, but overall it appears that this receptor is not related to the risk of developing distant metastases in triple-negative breast cancer [53]. Similar research efforts are warranted also for OC, to fully elucidate the role of hormone receptors as potential risk factors for BMs development.…”