Association of tumor‑infltrating lymphocytes with clinical outcomes in patients with triple‑negative breast cancer receiving neoadjuvant chemotherapy: a systematic review and meta‑analysis

Francisco Cezar Aquino de Moraes; María Eduarda Di Cavalcanti Alves de Souza; Vitor Kendi Tsuchiya Sano; Rachel Arantes Moraes; Ana C. Melo

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Association of tumor‑infltrating lymphocytes with clinical outcomes in patients with triple‑negative breast cancer receiving neoadjuvant chemotherapy: a systematic review and meta‑analysis

Francisco Cezar Aquino de Moraes ^[1] ; Maria Eduarda Cavalcanti Souza ^[2] ; Vitor Kendi Tsuchiya Sano ^[3] ; Rachel Arantes Moraes ^[4] ; Ana C. Melo ^[5]
1. [1] Universidad Federal de Pará
  
  Universidad Federal de Pará
  
  Brasil
2. [2] Universidade de Pernambuco
  
  Universidade de Pernambuco
  
  Brasil
3. [3] Universidade Federal do Acre
  
  Universidade Federal do Acre
  
  Brasil
4. [4] Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
5. [5] Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA
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Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 27, Nº. 3, 2025, págs. 974-987
Idioma: inglés
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Resumen
- Objective Triple-negative breast cancer (TNBC) presents a clinical challenge as an aggressive tumor, correlated with unfavorable prognosis. Tumor-infltrating lymphocytes (TILs) have garnered interest as a potential prognostic biomarker. However, the disparity in outcomes between varying TILs rates remains inadequately explored.
  
  Methods PubMed, Scopus, Web of Science, and Cochrane databases were searched for studies about the prognostic value of TILs in patients with TNBC receiving neoadjuvant chemotherapy. The hazard ratios (HRs) or odds ratios (ORs) were computed for binary endpoints, with 95% confdence intervals (CIs).
  
  Results Twenty-nine studies were included, involving a population of six thousand one hundred sixty-one (80.41%) with TNBC. The cut-of TILs value ranged from 10 to 60%, with 50% being the most related value. Compared with the low-TIL expression group, the disease-free survival (DFS) (HR 0.71; 95% CI 0.61–0.82; p<0.00001) and overall survival (OS) (HR 0.76; 95% CI 0.63–0.90; p=0.002) rates showed signifcant improvement with higher TIL infltrations. In the subgroup analyses of the lymphocyte subtypes CD4+and CD8+, there was statistical signifcance favoring higher TILs rates in both subtypes, each associated with improved DFS (HR 0.48; 95% CI 0.33–0.71; p=0.0002) and OS (HR 0.53; 95% CI 0.36–0.78; p=0.001), regardless of which cell subtype was predominantly infltrated. The complete pathological response analysis showed better rates for the higher TIL group than the control for both the TIL (OR 1.29; 95% CI 1.13–1.48; p=0.0003) and Ki-67 (OR 2.74; 95% CI 2.01–3.73; p<0.00001) analyses.
  
  Conclusion Higher expressions of TILs in patients with TNBC were associated with improved signifcantly DFS, OS, and pCR outcomes.