The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular Subtypes

Introduction: The antitumor host immune response is an important factor in breast cancer, but its role is not fully established. The role of tumor infiltrating lymphocytes (TIL) as an immunological biomarker in breast cancer has been significantly explored in recent years. The number of patients tre...

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Main Authors: Ionut Flaviu Faur, Amadeus Dobrescu, Adelina Ioana Clim, Paul Pasca, Catalin Prodan-Barbulescu, Bogdan Daniel Gherle, Cristi Tarta, Alexandru Isaic, Dan Brebu, Ciprian Duta, Bogdan Totolici, Gabriel Lazar
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/11/11/3037
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author Ionut Flaviu Faur
Amadeus Dobrescu
Adelina Ioana Clim
Paul Pasca
Catalin Prodan-Barbulescu
Bogdan Daniel Gherle
Cristi Tarta
Alexandru Isaic
Dan Brebu
Ciprian Duta
Bogdan Totolici
Gabriel Lazar
author_facet Ionut Flaviu Faur
Amadeus Dobrescu
Adelina Ioana Clim
Paul Pasca
Catalin Prodan-Barbulescu
Bogdan Daniel Gherle
Cristi Tarta
Alexandru Isaic
Dan Brebu
Ciprian Duta
Bogdan Totolici
Gabriel Lazar
author_sort Ionut Flaviu Faur
collection DOAJ
description Introduction: The antitumor host immune response is an important factor in breast cancer, but its role is not fully established. The role of tumor infiltrating lymphocytes (TIL) as an immunological biomarker in breast cancer has been significantly explored in recent years. The number of patients treated with neoadjuvant chemotherapy (NAC) has increased and the identification of a biomarker to predict the probability of pCR (pathological complete response) is a high priority. Materials and methods: We evaluated 334 cases of BC treated with NAC followed by surgical resection from 2020–2022 at the Ist Clinic of Oncological Surgery, Oncological Institute “Prof Dr I Chiricuta” Cluj Napoca. Of the above, 122 cases were available for histological evaluation both in pre-NAC biopsy and post-NAC resection tissue. Evaluation of biopsy fragments and resection parts were performed using hematoxylin eosin (H&E). The TIL evaluation took place according to the recommendations of the International TIL Working Group (ITILWG). Results: There was a strong association between elevated levels of pre-NAC TIL. At the same time, there is a statistically significant correlation between stromal TIL and tumor grade, the number of lymph node metastases, the molecular subtype and the number of mitoses (<i>p</i> < 0.005). Intratumoral TIL showed a significant correlation with tumor size, distant metastasis, molecular subtype, number of mitosis, stage and lymph node metastasis (<i>p</i> < 0.005). We also demonstrated that high pre-NAC STIL represents a strong predictive marker for pCR. Conclusion: This study reveals the role of TIL as a predictive biomarker in breast cancer not only for the well-established TNBC (triple negative breast cancer) and HER2+ (Her2 overexpressed) subtypes but also in Luminal A and B molecular subtypes. In this scenario, the evaluation of sTIL as a novel predictive and therapy-predicting factor should become a routinely performed analysis that could guide clinicians when choosing the most appropriate therapy.
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spelling doaj.art-390c26d5b9f940d4bfc6125df970ec332023-11-24T14:31:15ZengMDPI AGBiomedicines2227-90592023-11-011111303710.3390/biomedicines11113037The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular SubtypesIonut Flaviu Faur0Amadeus Dobrescu1Adelina Ioana Clim2Paul Pasca3Catalin Prodan-Barbulescu4Bogdan Daniel Gherle5Cristi Tarta6Alexandru Isaic7Dan Brebu8Ciprian Duta9Bogdan Totolici10Gabriel Lazar11IInd Surgery Clinic, Timisoara Emergency County Hospital, 300723 Timisoara, RomaniaIInd Surgery Clinic, Timisoara Emergency County Hospital, 300723 Timisoara, RomaniaIInd Obstetric and Gynecology Clinic “Dominic Stanca”, 400124 Cluj-Napoca, RomaniaIInd Surgery Clinic, Timisoara Emergency County Hospital, 300723 Timisoara, RomaniaIInd Surgery Clinic, Timisoara Emergency County Hospital, 300723 Timisoara, RomaniaDepartment of Plastic, Reconstructive and Aesthetic Surgery, Rennes University Hospital Center, Université de Rennes, 16 Boulevard de Bulgarie, 35000 Rennes, FranceIInd Surgery Clinic, Timisoara Emergency County Hospital, 300723 Timisoara, RomaniaIInd Surgery Clinic, Timisoara Emergency County Hospital, 300723 Timisoara, RomaniaIInd Surgery Clinic, Timisoara Emergency County Hospital, 300723 Timisoara, RomaniaIInd Surgery Clinic, Timisoara Emergency County Hospital, 300723 Timisoara, RomaniaIst Clinic of General Surgery, Arad County Emergency Clinical Hospital, 310158 Arad, RomaniaDepartment of Oncology Surgery, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, RomaniaIntroduction: The antitumor host immune response is an important factor in breast cancer, but its role is not fully established. The role of tumor infiltrating lymphocytes (TIL) as an immunological biomarker in breast cancer has been significantly explored in recent years. The number of patients treated with neoadjuvant chemotherapy (NAC) has increased and the identification of a biomarker to predict the probability of pCR (pathological complete response) is a high priority. Materials and methods: We evaluated 334 cases of BC treated with NAC followed by surgical resection from 2020–2022 at the Ist Clinic of Oncological Surgery, Oncological Institute “Prof Dr I Chiricuta” Cluj Napoca. Of the above, 122 cases were available for histological evaluation both in pre-NAC biopsy and post-NAC resection tissue. Evaluation of biopsy fragments and resection parts were performed using hematoxylin eosin (H&E). The TIL evaluation took place according to the recommendations of the International TIL Working Group (ITILWG). Results: There was a strong association between elevated levels of pre-NAC TIL. At the same time, there is a statistically significant correlation between stromal TIL and tumor grade, the number of lymph node metastases, the molecular subtype and the number of mitoses (<i>p</i> < 0.005). Intratumoral TIL showed a significant correlation with tumor size, distant metastasis, molecular subtype, number of mitosis, stage and lymph node metastasis (<i>p</i> < 0.005). We also demonstrated that high pre-NAC STIL represents a strong predictive marker for pCR. Conclusion: This study reveals the role of TIL as a predictive biomarker in breast cancer not only for the well-established TNBC (triple negative breast cancer) and HER2+ (Her2 overexpressed) subtypes but also in Luminal A and B molecular subtypes. In this scenario, the evaluation of sTIL as a novel predictive and therapy-predicting factor should become a routinely performed analysis that could guide clinicians when choosing the most appropriate therapy.https://www.mdpi.com/2227-9059/11/11/3037breast cancerTILmodified radical mastectomybreast conservative surgerypredictive biomarker
spellingShingle Ionut Flaviu Faur
Amadeus Dobrescu
Adelina Ioana Clim
Paul Pasca
Catalin Prodan-Barbulescu
Bogdan Daniel Gherle
Cristi Tarta
Alexandru Isaic
Dan Brebu
Ciprian Duta
Bogdan Totolici
Gabriel Lazar
The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular Subtypes
Biomedicines
breast cancer
TIL
modified radical mastectomy
breast conservative surgery
predictive biomarker
title The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular Subtypes
title_full The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular Subtypes
title_fullStr The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular Subtypes
title_full_unstemmed The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular Subtypes
title_short The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular Subtypes
title_sort value of tumor infiltrating lymphocytes til for predicting the response to neoadjuvant chemotherapy nac in breast cancer according to the molecular subtypes
topic breast cancer
TIL
modified radical mastectomy
breast conservative surgery
predictive biomarker
url https://www.mdpi.com/2227-9059/11/11/3037
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