66P Digital profiling of immune biomarkers: Relation to anthracycline benefit
Bibliographic record
Abstract
Recent studies have shown that the tumor microenvironment can shape the response to immune-modulating therapies. Anthracyclines are a major chemotherapy regimen for breast cancer that induce immunogenic cell death. We hypothesized that patients with “immune hot” tumors may benefit from anthracyclines more than patients with “immune cold” tumors. As one of the largest breast cancer studies using the GeoMx digital spatial profiling, we tested this hypothesis by profiling 35 biomarkers on 536 cases obtained from the Canadian Cancer Trials Group MA.5 phase III clinical trial. In this trial, node-positive breast cancer patients were randomized to receive either a cyclophosphamide-based (cyclophosphamide-methotrexate-fluorouracil (CMF)) or anthracycline-containing adjuvant chemotherapy (cyclophosphamide-epirubicin-fluorouracil (CEF)). Tissue microarray sections were stained with barcoded antibodies to obtain digitally quantified biomarker counts. Unsupervised hierarchical clustering revealed two patient clusters: immune infiltrated and ignored. Following a pre-specified statistical plan crafted to meet ReMARK (REporting recommendations for tumor MARKer prognostic studies) guidelines, we did not observe significant results for the primary hypotheses: Immune cluster assignment did not predict an improved 10-year relapse-free survival or overall survival for patients receiving CEF compared to CMF in the full cohort. However, some of our secondary hypotheses revealed a significant predictive value for immune cluster assignment and stromal tumor infiltrating lymphocytes assessed on hematoxylin and eosin (H&E)-stained sides for CEF benefit over CMF in the human epidermal growth factor receptor 2 (HER2)-enriched subset. As an exploratory analysis, supervised clustering of immune biomarkers suggested that low levels of TIM-3 and high levels of HLA-DR and PD-L1 were associated with an extra benefit from CEF compared with CMF. While novel multiplexing techniques provide a detailed insight into the tumor microenvironment, conventional H&E staining acts as a powerful tool to assess the value of immune microenvironment in predicting benefits from immunogenic chemotherapies.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".