173 Androgen receptor stratifies immune-cold triple negative breast cancer: meta-analysis of chemotherapy response to guide precision immunotherapy
Bibliographic record
Abstract
Background Up to one-third of triple-negative breast cancers (TNBC) express the androgen receptor (AR) and belong to the luminal-AR (LAR) subtype. These are characterised by low tumour-infiltrating lymphocytes (TILs) and muted interferon-γ signalling. Whether AR status should serve as a diagnostic stratifier for neoadjuvant chemotherapy and immunotherapy trials is unresolved. We performed a PRISMA-guided meta-analysis to quantify the effect of AR positivity (immunohistochemistry [IHC] ≥ 10%) on pathologic complete response (pCR) after neoadjuvant chemotherapy and synthesized immune-contexture data.Methods We performed a PRISMA-compliant systematic review and meta-analysis. MEDLINE, EMBASE, Scopus and ClinicalTrials.gov were searched (inception-31 May 2025; English) for TNBC neoadjuvant-chemotherapy studies that reported pathologic complete response (pCR) stratified by androgen-receptor (AR) expression (IHC ≥ 10%). Two reviewers screened 247 records, extracted AR-stratified pCR counts and relevant immune correlates, and assessed quality using the Newcastle-Ottawa Scale. Log-odds ratios were pooled using a DerSimonian-Laird random-effects model; heterogeneity was summarised by I 2. Inverse-variance weighting was used to estimate pooled prevalences of TIL-low (< 20% stromal tumour-infiltrating lymphocytes) and PD-L1 positivity (combined positive score ≥ 1) in AR-positive tumours.Results We analyzed eight studies including 1143 TNBC patients (262 AR-positive, 881 AR-negative). Only 12.3% of AR-positive tumours achieved a pathologic complete response (pCR), compared with 39.7% of AR-negative tumours. In pooled analysis, AR positivity was associated with an odds ratio of 0.25 (95% CI 0.13–0.48; I 2 = 31%), indicating a 75% lower likelihood of chemotherapy response in AR-positive tumours. Five studies (n = 723) reported immune correlates. 77% (95% CI 70–83%) of AR-positive tumours were TIL-low, compared with 32% (95% CI 26–38%) of AR-negative tumours. PD-L1 expression was observed in fewer than 10% of AR-positive tumours, versus 28–45% of AR-negative tumours. Gene expression analyses consistently showed down-regulation of antigen presentation and interferon-γ signaling in AR-positive TNBC, reinforcing its immune-cold phenotype.Conclusions AR positivity identifies a chemoresistant, immune-cold TNBC subtype with substantially lower pathologic complete response to standard neoadjuvant chemotherapy. Routine AR immunohistochemistry could serve as a predictive tissue biomarker to stratify patients—AR-positive tumours may warrant chemotherapy de-escalation and enrollment in trials combining androgen receptor antagonists with immune-priming or checkpoint blocking agents. Prospective studies incorporating AR status alongside TIL and PD-L1 assessment are needed to refine precision immunotherapy in triple-negative breast cancer.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.022 | 0.041 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.012 | 0.044 |
| Bibliometrics | 0.006 | 0.005 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".