Work

Efficacy and Safety of Androgen Receptor Pathway-Targeted Therapies in AR-Positive Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis

Year: 2026

Type: preprint

Study designs: Systematic Review, Meta-Analysis

Abstract: Background: Androgen receptor (AR)-positive triple-negative breast cancer (TNBC) represents a distinct molecular subtype driven by androgen signaling. However, existing clinical evidence is largely limited to small, early-phase single-arm trials with inconsistent endpoint definitions. This systematic review and meta-analysis evaluates the clinical activity and safety profile of AR pathway-targeted therapies in patients with AR-positive TNBC. Methods: PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were systematically searched from database inception through February 2026. Quantitative synthesis focused on patients with advanced or metastatic disease, using a random-effects generalized linear mixed model to pool objective response rates (ORR) and clinical benefit rates (CBR) at standardized timepoints (16 weeks and 6 months). Neoadjuvant studies were evaluated qualitatively. Results: Eleven studies met inclusion criteria (10 in advanced/metastatic settings, 1 neoadjuvant). Across nine advanced-disease studies (296 patients), the pooled ORR was 5.4% (95% CI: 3.3%–8.6%; I 2 = 0.0%). Standardized CBR was 30.7% (95% CI: 24.3%–37.9%) at 16 weeks (176 patients across 5 studies) and 19.6% (95% CI: 11.2%–32.1%) at 6 months (56 patients across 2 studies). In the neoadjuvant setting, 16.7% of patients achieved a pathological complete response. Safety outcomes were synthesized narratively due to varied reporting definitions. Conclusion: AR pathway-targeted therapies demonstrate limited direct tumor shrinkage but achieve durable disease control in nearly one-third of patients at standardized intervals. Given the reliance on small single-arm trials with varying AR positivity cutoffs, these findings represent signals of clinical activity rather than direct proof of superiority over standard treatments.

Source: Research Square

DOI: 10.21203/rs.3.rs-10998076/v1

Authors: Qiang Liu, Zhiyu Wu, Zhijing Liang

Institutions: Sun Yat-sen University, Sun Yat-sen Memorial Hospital, Peking University Third Hospital

Language: English

Topic: Breast Cancer Treatment Studies

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Sun Yat-sen University, National Science and Technology Major Project