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. 2020 Aug 19:10:1486.
doi: 10.3389/fonc.2020.01486. eCollection 2020.

Tumor-Infiltrating Lymphocytes (TILs) and Risk of a Second Breast Event After a Ductal Carcinoma in situ

Alberto Farolfi  1 , Elisabetta Petracci  2 , Luigi Serra  3 , Alessandra Ravaioli  4 , Sara Bravaccini  5 , Sara Ravaioli  5 , Maria Maddalena Tumedei  5 , Paola Ulivi  5 , Matteo Canale  5 , Maurizio Puccetti  6 , Fabio Falcini  4 , Secondo Folli  7 , Annalisa Curcio  8 , Andrea Rocca  1
Affiliations

Tumor-Infiltrating Lymphocytes (TILs) and Risk of a Second Breast Event After a Ductal Carcinoma in situ

Alberto Farolfi et al. Front Oncol. .

Abstract

Women with a diagnosis of ductal carcinoma in situ (DCIS) have a high risk of developing a second breast event (SBE). The immune system might play a role in trying to prevent a SBE. Patients diagnosed with DCIS were identified in the population-based cancer registry of Area Vasta Romagna from 1997 to 2010. Median follow-up is 8.5 years. Tumor-infiltrating lymphocytes (TILs) were evaluated both in index DCIS and in SBE. The main endpoint was to assess the association between TILs' levels in index DCIS and risk of a SBE. Out of 496 DCIS patients, 100 SBEs (20.2%) were identified: 55 ipsilateral (11.1%) and 43 contralateral (8.7%). The distribution of TILs was heterogeneous, but significantly associated with grade, necrosis, screen detection and type of surgery. Patients stratified according to TILs percentage (≤5% and >5%) did not show a statistically significant difference in the 5-year cumulative incidence of SBEs: 14.9% (95% CI 11.3-19.1) and 11.0% (95% CI, 6.9-16.2), respectively (p = 0.147). In the subgroup of patients who did not receive radiotherapy, TILs >5% were associated with a reduced risk of SBE (HR 0.34, 95% CI 0.14-0.82, p = 0.016). Although we did not find any significant association between TILs and SBE, further studies evaluating their role according to radiotherapy are warranted.

Keywords: breast conserving surgery; ductal carcinoma in situ; radiotherapy; second breast event; tumor infiltrating lymphocytes; tumor recurrence.

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Figures

Figure 1
Figure 1
Examples of distribution of tumor-infiltrating lymphocytes (TILs) on hematoxylin-eosin section of ductal carcinoma in situ (DCIS) at different magnifications (5x and 10x). (A) TIL = 0%; (B) TIL = 1%; (C) TIL = 5%; (D) TIL = 10%; (E) TIL = 20%; (F) TIL = 40%; (G) TIL = 50%; (H) TIL = 70%.
Figure 2
Figure 2
Distribution of patients by grade and treatment.
Figure 3
Figure 3
Cumulative incidences of IBEs (A) and CBEs (B).
Figure 4
Figure 4
Waterfall plot of TILs variation between primary DCIS and SBE (A), IBE (B), or CBE (C).
See this image and copyright information in PMC

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