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. 2022 Nov 30:12:999843.
doi: 10.3389/fonc.2022.999843. eCollection 2022.

Expression patterns and prognostic implications of tumor-infiltrating lymphocytes dynamics in early breast cancer patients receiving neoadjuvant therapy: A systematic review and meta-analysis

Yajing Zhu  1 , Evangelos Tzoras  1 , Alexios Matikas  1   2 , Jonas Bergh  1   2 , Antonios Valachis  3 , Ioannis Zerdes  1   2 , Theodoros Foukakis  1   2
Affiliations

Expression patterns and prognostic implications of tumor-infiltrating lymphocytes dynamics in early breast cancer patients receiving neoadjuvant therapy: A systematic review and meta-analysis

Yajing Zhu et al. Front Oncol. .

Abstract

Purpose: High levels of tumor-infiltrating lymphocytes (TILs) are associated with better outcomes in early breast cancer and higher pathological response rates to neoadjuvant chemotherapy especially in the triple-negative (TNBC) and HER2+ subtypes. However, the dynamic changes in TILs levels after neoadjuvant treatment (NAT) are less studied. This systematic review and meta-analysis aimed to investigate the patterns and role of TILs dynamics change in early breast cancer patients receiving NAT.

Methods: Medline, Embase, Web of Science Core Collection and PubMed Central databases were searched for eligible studies. Data were extracted independently by two researchers and discordances were resolved by a third. Pooled TILs rates pre- & post-treatment (overall and per subtype), pooled rates of ΔTILs and direction of change after NAT as well as correlation of ΔTILs with survival outcomes were generated in the outcome analysis.

Results: Of 2116 identified entries, 34 studies fulfilled the criteria and provided adequate data for the outcomes of interest. A decreased level of TILs was observed after NAT in paired samples across all subtypes. The effect of NAT on TILs was most prominent in TNBC subtype with a substantial change, either increase or decrease, in 79.3% (95% CI 61.7-92.6%) of the patients as well as in HER2+ disease (14.4% increased vs 46.2% decreased). An increase in ΔTILs in TNBC was associated with better disease-free/relapse-free survival in pooled analysis (univariate HR = 0.59, 95% CI: 0.37-0.95, p = 0.03).

Conclusion: This meta-analysis illustrates the TILs dynamics during NAT for breast cancer and indicates prognostic implications of ΔTILs in TNBC. The potential clinical utility of the longitudinal assessment of TILs during neoadjuvant therapy warrants further validation.

Keywords: TILs dynamics; biomarker; breast cancer; neoadjuvant treatment; prognosis; tumor-infiltrating lymphocytes (TILs).

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Conflict of interest statement

JB receives research funding from Merck paid to Karolinska Institutet and from Amgen, Bayer, Pfizer, Roche and Sanofi-Aventis paid to Karolinska University Hospital. No personal payments. Payment from UpToDate for a chapter in breast cancer prediction paid to Asklepios Medicine HB. TF: institutional research grants from Roche and Pfizer, institutional fees from Roche, Pfizer and Astra Zeneca and personal fees from Affibody, Novartis, Pfizer, Roche, Exact Sciences, Veracyte and UpToDate. AM: consultancy to Veracyte no financial or other compensation, AV: institutional research grant from Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow Diagram of search and study selection in this meta-analysis.
Figure 2
Figure 2
Forest-plots on Standardized mean difference (SMD) of Tumor-Infiltrating Lymphocytes (TILs) pre- and post-treatment per breast cancer subtype (A) not specified (B) HER2-positive (C) Triple-negative breast cancer [TNBC] and (D) Disease-free survival [DFS]/Recurrence-free survival [RFS] according to TILs change in TNBC subtype.
See this image and copyright information in PMC

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