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-g signalling.Whether AR status should serve as a diagnostic stratifier for neoadjuvant chemotherapy and immunotherapy trials is unresolved.We performed a PRISMA-guided metaanalysis 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 Clinical-Trials.govwere 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. ResultsWe 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 downregulation of antigen presentation and interferon-g signaling in AR-positive TNBC, reinforcing its immune-cold phenotype.Conclusions AR positivity identifies a chemoresistant, immunecold 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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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 teacher head, 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".