TY - JOUR
TI - Prognostic impact of stromal and intratumoral CD3, CD8 and FOXP3 in adjuvantly treated breast cancer: do they add information over stromal tumor-infiltrating lymphocyte density?
AU - Koletsa, T.
AU - Kotoula, V.
AU - Koliou, G.-A.
AU - Manousou, K.
AU - Chrisafi, S.
AU - Zagouri, F.
AU - Sotiropoulou, M.
AU - Pentheroudakis, G.
AU - Papoudou-Bai, A.
AU - Christodoulou, C.
AU - Xepapadakis, G.
AU - Zografos, G.
AU - Petraki, K.
AU - Pazarli, E.
AU - Koutras, A.
AU - Kourea, H.P.
AU - Bafaloukos, D.
AU - Chatzopoulos, K.
AU - Iliadis, A.
AU - Markopoulos, C.
AU - Venizelos, V.
AU - Arnogiannaki, N.
AU - Kalogeras, K.T.
AU - Kostopoulos, I.
AU - Gogas, H.
AU - Fountzilas, G.
JO - Cancer Immunology, Immunotherapy
PY - 2020
VL - 69
TODO - 8
SP - 1549-1564
PB - Springer-Verlag
SN - 0340-7004, 1432-0851
TODO - 10.1007/s00262-020-02557-0
TODO - antineoplastic agent;  CD3 antigen;  CD8 antigen;  epirubicin;  paclitaxel;  transcription factor FOXP3;  CD3 antigen;  CD8 antigen;  forkhead transcription factor;  FOXP3 protein, human;  tumor marker, adjuvant therapy;  adult;  aged;  Article;  breast cancer;  cancer combination chemotherapy;  cancer grading;  cancer prognosis;  cancer recurrence;  cell density;  cell proliferation;  controlled study;  female;  follow up;  human;  human cell;  human epidermal growth factor receptor 2 positive breast cancer;  human tissue;  immunohistochemistry;  luminal A breast cancer;  luminal B breast cancer;  lymphocyte subpopulation;  major clinical study;  priority journal;  prognostic assessment;  randomized controlled trial;  stroma cell;  tissue microarray;  triple negative breast cancer;  tumor associated leukocyte;  adjuvant chemotherapy;  adjuvant radiotherapy;  breast tumor;  immunology;  metabolism;  middle aged;  pathology;  prognosis;  tumor associated leukocyte;  young adult, Adult;  Aged;  Biomarkers, Tumor;  Breast Neoplasms;  CD3 Complex;  CD8 Antigens;  Chemotherapy, Adjuvant;  Female;  Follow-Up Studies;  Forkhead Transcription Factors;  Humans;  Lymphocyte Subsets;  Lymphocytes, Tumor-Infiltrating;  Middle Aged;  Prognosis;  Radiotherapy, Adjuvant;  Stromal Cells;  Young Adult
TODO - Background: Tumor-infiltrating lymphocytes (TILs) and their subsets contribute to breast cancer prognosis. We investigated the prognostic impact of CD3+, CD8+ and FOXP3+ TILs in patients with early intermediate/high-risk breast cancer treated with adjuvant anthracycline-based chemotherapy within two randomized trials conducted by our Group. Methods: We examined 1011 patients (median follow-up 130.9 months) and their tumors for total, stromal (s) and intratumoral (i) CD3, CD8 and FOXP3 lymphocyte density (counts/mm2) on tissue-microarray cores by immunohistochemistry. Morphological sTIL density on whole H&E-stained sections was also evaluated. Results: The majority of TILs were CD3+. Total CD3 and CD8, sCD3 and sCD8, iCD3 and iCD8, sFOXP3 and iFOXP3 were strongly correlated (Spearman’s rho values > 0.6). High individual lymphocytic subsets and sTIL density were strongly associated with high tumor grade, higher proliferation and HER2-positive and triple-negative tumors (all p values < 0.001). Higher sTIL density (10% increments), high density of almost each individual marker and all-high profiles conferred favorable prognosis. However, when adjusted for sTIL density, stromal and intratumoral lymphocytic subsets lost their prognostic significance, while higher sTIL density conferred up to 15% lower risk for relapse. Independently of sTIL density, higher total CD3+ and CD8+ TILs conferred 35% and 28% lower risk for relapse, respectively. Conclusions: Stromal and intratumoral CD3+, CD8+ and FOXP3+ TIL density do not seem to add prognostic information over the morphologically assessed sTIL density, which is worth introducing in routine histology reports. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
ER -