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
. 2022 Oct 18;12(10):2527.
doi: 10.3390/diagnostics12102527.

Prognostic Value of Tumour-Infiltrating Lymphocytes in an Unselected Cohort of Breast Cancer Patients

Kathleen Schüler  1 , Daniel Bethmann  2 , Sandy Kaufhold  1 , Carolin Hartung  1 , Kathrin Stückrath  1 , Tilmann Lantzsch  3 , Christoph Uleer  4 , Volker Hanf  5 , Susanne Peschel  6 , Jutta John  7 , Marleen Pöhler  8 , Jörg Buchmann  9 , Karl-Friedrich Bürrig  10 , Edith Weigert  11 , Christoph Thomssen  1 , Eva Johanna Kantelhardt  1   12 , Martina Vetter  1
Affiliations

Prognostic Value of Tumour-Infiltrating Lymphocytes in an Unselected Cohort of Breast Cancer Patients

Kathleen Schüler et al. Diagnostics (Basel). .

Abstract

Tumour-infiltrating lymphocytes (TILs) are considered to have prognostic and predictive value for patients with early breast cancer. We examined 1166 breast cancer patients from a prospective, multicentre cohort (Prognostic Assessment in Routine Application (PiA), n = 1270, NCT01592825) following recommendations from the International TILs Working Group. TIL quantification was performed using predefined groups and as a continuous variable in 10% increments. The primary objective was the distribution of TILs in different breast cancer types. The second objective was the association with the recurrence-free interval (RFI) and overall survival (OS). Stromal infiltration with more than 60% TILs appeared in 2% of hormone receptor (HR)-positive and HER2-negative tumours, in 9.8% of HER2-positive tumours (any HR) and 19.4% of triple-negative breast cancers (TNBCs). Each 10% increment was associated with an improvement in the prognosis in HER2-positive samples (RFI, hazard ratio 0.773, 95% CI 0.587-1.017; OS, hazard ratio 0.700, 95% CI 0.523-0.937). When defining exploratory cut-offs for TILs, the use of a 30% threshold for the HR-positive and HER2-negative group, a 20% threshold for the HER2 group and a 60% threshold for the TNBC group appeared to be the most suitable. TILs bore prognostic value, especially in HER2-positive breast cancer. For clinical use, additional research on the components of immune infiltration might be reasonable.

Keywords: cohort study; early breast cancer; prognosis; tumor infiltrating lymphocytes.

PubMed Disclaimer

Conflict of interest statement

C.T. reports support from Martin Luther University, Arbeitsgemeinschaft Gynäkologische Onkologie e.V., Sanofi-Aventis, American Diagnostica and BIOMED BMH4-98-9418, as well as honoraria from Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, Gilead, Lilly, MSD, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Sanofi-Aventis, Roche, Vifor, Hexal, Mylan and Seagen. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. The other authors have no relevant financial or non-financial interests to disclose.

Figures

Figure 1
Figure 1
CONSORT diagram: patients with TIL evaluations (n = 1166) and in the subgroups according to HR and HER2 expressions. Abbreviations: hormone receptor (HR), human epidermal growth factor receptor 2 (HER2), triple-negative breast cancer (TNBC).
Figure 2
Figure 2
Distributions of TILs (n = 1166).
Figure 3
Figure 3
Forest plot for the effect of TILs infiltration per 10% increment in different receptor groups regarding the RFI. Red box: point estimate of the effect for a single group, diamond: overall effect estimate of all groups.
Figure 4
Figure 4
Kaplan–Meier plots for patients in the TILs groups with their cut-offs for the HR-pos and HER2-neg RFI (A) and OS (B), HER2-pos and any HR RFI (C) and OS (D), and TNBC RFI (E) and OS (F); the tables present the effective sample size for each interval (no. at risk).
See this image and copyright information in PMC

References

    1. Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013. - DOI - PubMed
    1. Dieci M., Miglietta F., Guarneri V. Immune Infiltrates in Breast Cancer: Recent Updates and Clinical Implications. Cells. 2021;10:223. doi: 10.3390/cells10020223. - DOI - PMC - PubMed
    1. Baxevanis C.N., Sofopoulos M., Fortis S.P., Perez S.A. The role of immune infiltrates as prognostic biomarkers in patients with breast cancer. Cancer Immunol. Immunother. 2019;68:1671–1680. doi: 10.1007/s00262-019-02327-7. - DOI - PMC - PubMed
    1. Salgado R., Denkert C., Demaria S., Sirtaine N., Klauschen F., Pruneri G., Wienert S., van den Eynden G., Baehner F.L., Penault-Llorca F., et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: Recommendations by an International TILs Working Group 2014. Ann. Oncol. 2015;26:259–271. doi: 10.1093/annonc/mdu450. - DOI - PMC - PubMed
    1. Savas P., Caramia F., Teo Z.L., Loi S. Oncogene addiction and immunity. Curr. Opin. Oncol. 2014;26:562–567. doi: 10.1097/CCO.0000000000000131. - DOI - PubMed

LinkOut - more resources