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. 2022 Aug 13;14(16):3916.
doi: 10.3390/cancers14163916.

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

Sunil S Badve  1   2 , Sanghee Cho  3 , Xiaoyu Lu  4 , Sha Cao  4 , Soumya Ghose  3 , Aye Aye Thike  5 , Puay Hoon Tan  6 , Idris Tolgay Ocal  7 , Daniele Generali  8 , Fabrizio Zanconati  8 , Adrian L Harris  9 , Fiona Ginty  3 , Yesim Gökmen-Polar  1   2
Affiliations

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

Sunil S Badve et al. Cancers (Basel). .

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.

Keywords: breast cancer; ductal carcinoma in situ; ethnicity; tumor infiltrating lymphocytes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Correlation analysis of tumor-infiltrating lymphocytes (TILs) assessments with clinical and histologic parameters. The dependence of each pair was evaluated by Fishers exact test, and adjusted p (FDR) = 0.1 was applied to 36 pairs; p-value was adjusted using Bonferroni-Holm procedure; Blue and red circles represent positive and negative correlations, respectively; Significance levels were shown based on the size of the circles.
Figure 2
Figure 2
Correlation analysis of tumor-infiltrating lymphocytes (TILs) assessment with clinical outcome; (A) Kaplan-Meier (KM) plots for 5-year recurrence-free survival according TILs assessments and clinical parameters (univariable analysis). The significant associations were shown in the figure; (B) A forest plot showing the hazard ratio and 95% confidence intervals associated with variables and the primary endpoint (5 year recurrence); Circles represent the hazard ratio and the horizontal bars extend from; abbreviations- Grade-Int, Grade intermediate; HR-Hormone receptor status.
Figure 3
Figure 3
Forest plot of multivariable analysis of cohorts for tumor-infiltrating lymphocytes (TILs) assessments with clinical and histologic parameters. In total 3 variables were selected—age, grade, and circumferential TILs with significance (Wald test p = 0.01).
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