Prognostic relevance of tumor‑infiltrating lymphocytes in residual tumor tissue from patients with triple‑negative breast cancer following neoadjuvant chemotherapy: A systematic review and meta‑analysis
Why this work is in the frame
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Bibliographic record
Abstract
Further adjuvant chemotherapy treatment can provide benefits to certain patients with triple‑negative breast cancer (TNBC) that fail to achieve pathological complete response (pCR) after the administration of a neoadjuvant chemotherapy (NAC) regimen. However, biomarkers suitable for identifying patients likely to experience poor prognostic outcomes after undergoing additional adjuvant chemotherapy are currently lacking. Accordingly, the present meta‑analysis was conducted to explore the relationship between tumor‑infiltrating lymphocytes (TILs) or TIL subtypes (CD4<sup>+</sup> or CD8<sup>+</sup>) in residual tumor (RT) tissue following NAC and TNBC patient prognosis. Relevant studies published through March 2023 were identified in Pubmed, The Cochrane Library, Embase and Web of Science databases. After excluding irrelevant studies, data were extracted from the remaining reports, while study quality was analyzed with the Newcastle‑Ottawa Scale. Subsequent analyses were performed with Stata 14.0 and Review Manager 5.3. In total, seven relevant studies incorporating 1,202 patients were identified, all of which were retrospective cohort studies. Pooled analyses demonstrated that those patients exhibiting higher levels of RT TIL infiltration following NAC exhibited significantly improved recurrence‑free, metastasis‑free and event‑free survival (RFS/MFS/EFS) compared with patients with lower RT TIL infiltration levels, together with an improved distant recurrence‑free interval (DRFI) [hazard ratio (HR)=0.52; 95% confidence interval (CI)=0.39‑0.69; P<0.00001]. In addition, patients exhibiting high RT TIL infiltration exhibited improved overall survival (OS) and breast cancer‑specific survival (BCSS; HR=0.49; 95% CI=0.38‑0.65; P<0.00001). Additional subgroup analyses revealed that patients with higher TIL infiltration levels or TIL subtype (CD4<sup>+</sup> or CD8<sup>+</sup>) infiltration exhibited improved RFS/MFS/EFS/DRFI as compared with patients with lower levels of overall TIL or TIL subtype (CD4<sup>+</sup> or CD8<sup>+</sup>) infiltration in RT tissue (HR=0.35, 95% CI=0.20‑0.59, P<0.0001; HR=0.49, 95% CI=0.33‑0.71, P=0.0002). Consistently, the OS/BCSS of patients exhibiting high levels of overall TIL or TIL subtype (CD4<sup>+</sup> or CD8<sup>+</sup>) infiltration was increased compared with patients with lower levels of such infiltration (HR=0.33, 95% CI=0.19‑0.59, P=0.0002; HR=0.55, 95% CI=0.41‑0.76, P=0.0002). These data thus demonstrate that levels of overall TIL infiltration or infiltration by CD4<sup>+</sup> or CD8<sup>+</sup> TILs in RT following NAC can be used as a biomarker to reliably predict prognostic outcomes in patients with TNBC, in addition to highlighting possible targets that may guide the further immunotherapeutic management of these patients.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.010 | 0.001 |
| Bibliometrics | 0.000 | 0.002 |
| 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 it