Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Oct:59:183-192.
doi: 10.1016/j.breast.2021.07.007. Epub 2021 Jul 9.

Tumour-infiltrating lymphocytes in non-invasive breast cancer: A systematic review and meta-analysis

Rafael Caparica  1 , Marco Bruzzone  2 , Elisa Agostinetto  3 , Maria Alice Franzoi  1 , Marcello Ceppi  2 , Nina Radosevic-Robin  4 , Frédérique Penault-Llorca  4 , Karen Willard-Gallo  5 , Sherene Loi  6 , Roberto Salgado  7 , Evandro de Azambuja  1
Affiliations
Meta-Analysis

Tumour-infiltrating lymphocytes in non-invasive breast cancer: A systematic review and meta-analysis

Rafael Caparica et al. Breast. 2021 Oct.

Abstract

Background: The role of tumour infiltrating lymphocytes (TILs) as a biomarker in non-invasive breast cancer is unclear. This meta-analysis assessed the prognostic impact of TIL levels in patients with non-invasive breast cancer.

Methods: Systematic literature search was performed to identify studies assessing local recurrence in patients with non-invasive breast cancer according to TIL levels (high vs. low). Subgroup analyses per local recurrence (invasive and non-invasive) were performed. Secondary objectives were the association between TIL levels and non-invasive breast cancer subtypes, age, grade and necrosis. Odds ratios (ORs) and 95% confidence intervals (CI) were extracted from each study and a pooled analysis was conducted with random-effect model.

Results: Seven studies (N = 3437) were included in the present meta-analysis. High-TILs were associated with a higher likelihood of local recurrence (invasive or non-invasive, N = 2941; OR 2.05; 95%CI, 1.03-4.08; p = 0.042), although with a lower likelihood of invasive local recurrence (N = 1722; OR 0.69; 95%CI, 0.49-0.99; p = 0.042). High-TIL levels were associated with triple-negative (OR 3.84; 95%CI, 2.23-6.61; p < 0.001) and HER2-positive (OR 6.27; 95%CI, 4.93-7.97; p < 0.001) subtypes, high grade (OR 5.15; 95%CI, 3.69-7.19; p < 0.001) and necrosis (OR 3.09; 95%CI, 2.33-4.10; p < 0.001).

Conclusions: High-TIL levels were associated with more aggressive tumours, a higher likelihood of local recurrence (invasive or non-invasive) but a lower likelihood of invasive local recurrence in patients with non-invasive breast cancer.

Keywords: “Local recurrence”; “Non-invasive breast cancer”; “Tumour infiltrating lymphocytes”.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest RC received speaker honoraria from Boehringer-Ingelheim, AstraZeneca, and Janssen; and travel grants from Pfizer and AstraZeneca, none related to the present work. EdA has received honoraria from Roche-Genentech, Libbs, Seattle Genetics, Novartis, Pierre Fabre; research grant from Roche-Genentech, Astra Zeneca, GSK/Novartis, Servier (to the institution), and travel grants from Roche-Genentech and GlaxoSmithKline, none related to the present work. All other authors declare no disclosures related to the present work. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
PRISMA diagram illustrating literature search and study selection for this meta-analysis. Abbreviations: ASCO, American Society of Clinical Oncology; BC, breast cancer; ESMO, European Society for Medical Oncology; SABCS, San Antonio Breast Cancer Symposium; TILs, tumor infiltrating lymphocytes.
Fig. 2
Fig. 2
Forest plots and the pooled odds ratios with the respective p values for local recurrence according to TILs levels. Abbreviations: OR, odds ratio; CI, confidence intervals; TILs, tumor infiltrating lymphocytes.
Fig. 3
Fig. 3
Forest plots and the pooled odds ratios with the respective p values for invasive local recurrence (A) and non-invasive local recurrence (B) according to TILs levels. Abbreviations: OR, odds ratio; CI, confidence intervals; TILs, tumor infiltrating lymphocytes.
Fig. 4
Fig. 4
Forest plots and the pooled odds ratios with the respective p values for the association between triple-negative (A), HER2-positive (B) and luminal (C) breast cancer subtypes and TILs levels. Abbreviations: OR, odds ratio; CI, confidence intervals; TILs, tumor infiltrating lymphocytes.
Fig. 5
Fig. 5
Forest plots and the pooled odds ratios with the respective p values for the association between age (A), histological grade (B) and necrosis (C) and TILs levels. Abbreviations: OR, odds ratio; CI, confidence intervals; TILs, tumor infiltrating lymphocytes.
See this image and copyright information in PMC

References

    1. Lee R.J., Vallow L.A., McLaughlin S.A., Tzou K.S., Hines S.L., Peterson J.L. Ductal carcinoma in situ of the breast. Int J Surg Oncol. 2012;2012:123549. doi: 10.1155/2012/123549. - DOI - PMC - PubMed
    1. Ernster V.L., Ballard-Barbash R., Barlow W.E., Zheng Y., Weaver D.L., Cutter G. Detection of ductal carcinoma in situ in women undergoing screening mammography. J Natl Cancer Inst. 2002;94:1546–1554. doi: 10.1093/jnci/94.20.1546. - DOI - PubMed
    1. Narod S.A., Iqbal J., Giannakeas V., Sopik V., Sun P. Breast cancer mortality after a diagnosis of ductal carcinoma in situ. JAMA Oncol. 2015;1:888–896. doi: 10.1001/jamaoncol.2015.2510. - DOI - PubMed
    1. Giannakeas V., Sopik V., Narod S.A. Association of a diagnosis of ductal carcinoma in situ with death from breast cancer. JAMA Netw Open. 2020;3:e2017124. doi: 10.1001/jamanetworkopen.2020.17124. - DOI - PMC - PubMed
    1. Chen X.-Y., Yeong J., Thike A.A., Bay B.H., Tan P.H. Prognostic role of immune infiltrates in breast ductal carcinoma in situ. Breast Canc Res Treat. 2019;177:17–27. doi: 10.1007/s10549-019-05272-2. - DOI - PubMed

Substances