Tumor Infiltrating Lymphocytes in Multi-National Cohorts of Ductal Carcinoma In Situ (DCIS) of Breast

• Type of Material: Article
• Authors: Sunil Badve, Emory University; Sanghee Cho, GE Global Research Center; Xiaoyu Lu, Indiana University; Sha Cao, Indiana University; Soumya Ghose, GE Global Research Center; Aye Aye Thike, Singapore General Hospital; Puay Hoon Tan, Singapore General Hospital; Idris Tolgay Ocal, Mayo Clinic Arizona; Daniele Generali, University of Trieste; Fabrizio Zanconati, University of Trieste; Adrian L. Harris, Oxford University; Fiona Ginty, GE Global Research Center; Yesim Polar, Emory University
• Language: English
• Date: 2022-08-13
• Publisher: MDPI AG
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cancers14163916
• Title of Journal or Parent Work: Cancers
• Volume: 14
• Issue: 16
• Grant/Funding Information: This study is supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA194600 to S Badve, and F Ginty. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: breast cancer; ductal carcinoma in situ; tumor infiltrating lymphocytes; ethnicity
• Research Categories: Sociology, Ethnic and Racial Studies; Health Sciences, Oncology

Abstract

Tumor-infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer. However, their prognostic significance in ductal carcinoma in situ (DCIS) has been controversial. To investigate the prognostic role of TILs in DCIS outcome, we used different scoring methods for TILs in multi-national cohorts from Asian and European women. Self-described race was genetically confirmed using QC Infinium array combined with radmixture software. Stromal TILs, touching TILs, circumferential TILs, and hotspots were quantified on H&E-stained slides and correlated with the development of second breast cancer events (BCE) and other clinico-pathological variables. In univariate survival analysis, age older than 50 years, hormone receptor positivity and the presence of circumferential TILs were weakly associated with the absence of BCE at the 5-year follow-up in all cohorts (p < 0.03; p < 0.02; and p < 0.02, respectively, adjusted p = 0.11). In the multivariable analysis, circumferential TILs were an independent predictor of a better outcome (Wald test p = 0.01), whereas younger age was associated with BCE. Asian patients were younger with larger, higher grade, HR negative DCIS lesions, and higher TIL variables. The spatial arrangement of TILs may serve as a better prognostic indicator in DCIS cases than stromal TILs alone and may be added in guidelines for TILs evaluation in DCIS.