Locally advanced breast cancer: Tumor-infiltrating lymphocytes as a predictive factor of response to neoadjuvant chemotherapy

Russo, Leonardo; Maltese, Anggela; Betancourt, Luís; Romero, Gabriel; Cialoni, Daniela; Fuente, Liliana De la; Gutierrez, Marianna; Ruiz, Ángela Salmerón; Agüero, E; Hernández, Sílvia

doi:10.1016/j.ejso.2019.01.222

Cited by 29 publications

(22 citation statements)

References 18 publications

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“…In another study evaluating baseline biopsies prior to chemotherapy, where both areas of stroma infiltrated by lymphocytes (proportional score) and intensity of lymphatic infiltration (intensity score) were taken into consideration, high TILs score was associated with pCR in TNBC but not for Her2+ or HR+ tumors (43). Other retrospective cohorts evaluating pre-NAC TILs association with pCR similarly failed to find a significant correlation, most likely due to the limited number of HR+ tumors used in pCR prediction (44,45,60). The significance of TILs in patients treated with neoadjuvant hormonal therapy has been recently studied as part of a nationwide phase II trial conducted by the Danish Breast Cancer Group.…”

Section: Tils In Breast Tumors Before and After Neoadjuvant Systemic Therapymentioning

confidence: 99%

The Immunology of Hormone Receptor Positive Breast Cancer

et al. 2021

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Immune checkpoint blockade (ICB) has revolutionized the treatment of cancer patients. The main focus of ICB has been on reinvigorating the adaptive immune response, namely, activating cytotoxic T cells. ICB has demonstrated only modest benefit against advanced breast cancer, as breast tumors typically establish an immune suppressive tumor microenvironment (TME). Triple-negative breast cancer (TNBC) is associated with infiltration of tumor infiltrating lymphocytes (TILs) and patients with TNBC have shown clinical responses to ICB. In contrast, hormone receptor positive (HR+) breast cancer is characterized by low TIL infiltration and minimal response to ICB. Here we review how HR+ breast tumors establish a TME devoid of TILs, have low HLA class I expression, and recruit immune cells, other than T cells, which impact response to therapy. In addition, we review emerging technologies that have been employed to characterize components of the TME to reveal that tumor associated macrophages (TAMs) are abundant in HR+ cancer, are highly immune-suppressive, associated with tumor progression, chemotherapy and ICB-resistance, metastasis and poor survival. We reveal novel therapeutic targets and possible combinations with ICB to enhance anti-tumor immune responses, which may have great potential in HR+ breast cancer.

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Section: Tils In Breast Tumors Before and After Neoadjuvant Systemic Therapymentioning

confidence: 99%

The Immunology of Hormone Receptor Positive Breast Cancer

et al. 2021

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“…1). Finally, 11 potentially eligible RCTs [33][34][35][36][37][38][39][40][41][42]54] and 11 case-control studies [43][44][45][46][47][48][49][50][51][52][53] were considered, consisting of approximately 8 052 participants. The population of patients in each study varied from 50 to 1 060 cases, and the follow-up time ranged from 3.4 to 120 months.…”

Section: Search Results and Characteristics Of Eligible Studiesmentioning

confidence: 99%

Predictive Value of Tumor Infiltrating Lymphocytes in Neoadjuvant Chemotherapy Treated Breast Cancer: A Meta-Analysis of 8052 Patients

Li¹,

Zhang²,

Wang³

et al. 2020

Preprint

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Background: We conducted a meta-analysis to determine the prognostic value of Tumor infiltrating lymphocytes (TILs) for patients with breast cancer on Neoadjuvant Chemotherapy, to explore the prognostic value of different TILs threshold in terms of pathological complete response (PCR).Methods: A systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible articles published before September 2020. Data from studies were analyzed by using Review Manager 5.3 and Stata 15.0Results: A total of 22 published studies (including 8 052 patients) were eligible. Patients with high TILs level showed a higher rate of PCR to treatment (OR=3.182, 95 %CI, 2.549-3.973) compared to breast cancer patients with low TILs level. Although the association of TILs with response to neoadjuvant chemotherapy was similar across most breast cancer subtypes, there were a few differences ER negative or ER positive breast cancer. In studies (Type of breast cancer not clearly classified in the literature) where the cut-off value for TILs was ≥10 %, higher levels of total TILs predicted a higher PCR rate of Neoadjuvant Chemotherapy. However, for HER2-positive breast cancer patients, when a cut-off valve of TILs ≥ 30 % was used, the OR was 2.631 (95 % CI, 1.739-3.982, P = 0.000). TILs also were related to better DFS (HR=0.95, 95 %CI, 0.92-0.98, P=0.000) and overall survival (OS) (HR=0.90, 95 %CI, 0.85-0.95, P<0.0001) after Neoadjuvant Chemotherapy.Conclusions: TILs can be used as predictors of patients with breast cancer on Neoadjuvant Chemotherapy. TILs threshold with the greatest prognostic significance of PCR is as yet unknown, but a TILs threshold of at least 30 % is associated with the most powerful outcome prognostication of PCR.

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“…TheacronymTILshasbeenusedformanyyears, mainly in association with malignant melanoma [11].Itisdescribedasthehostrelatedprognostic factorinthelatestTNM8skinmelanomareferences, together with the melanoma thickness, mitotic activity,surfaceulcerationandtheextentofmetastaticdisease [4].TILshavebeenextensivelystudiedin association with many solid malignancies, both as aprognosticandpredictivefactor.Atpresent,besides melanoma,themostadvancedstudiesofTILsarein breastcancer,asprognostic [26] andpredictivefactors [27],withonlystromalTILsbeingconsideredas havingsuchprognosticvalue [26].…”

Section: Discussionmentioning

confidence: 99%

The prognostic significance of tumour infiltrating lymphocytes in oral squamous cell carcinoma

Książek

Lewandowski²,

Brodowski³

et al. 2019

pjp

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Currentlythereisbeingconductedanextensivesearchtofindnewprognosticfactorsinoralsquamouscellcarcinomawhichwouldassistinbetterpatientmanagement.Oneofthemostpromisingprognosticmarkersisthedensityoftumourinfiltratinglymphocytes.100casesofpatientswithoralsquamouscellcarcinomathat underwentsurgicalresectionbetween2006andJune2016atourinstitutionwere included in this study. From each case the most representative HE stained slide wasidentifiedandthedensityoftumourinfiltratinglymphocyteswereclassified asnon-briskorbrisk,whichwasincludedinthesurvivalanalysis.Uponanalysis therewasastrongcorrelationbetweennon-brisk(n=28)andbrisk(n=72)tumourinfiltratinglymphocytesandtheprimaryclinicaloutcomes:overallsurvival (p = 0.0472) and local recurrence-free survival (p = 0.00037). Univariate and multivariateCoxregressionmodelconfirmedthehighprognosticvalueoftumour infiltratinglymphocytesastheindependentprognosticindicatorofbettersurvival, beingevensuperior,inourstudy,tothetraditionalpTNMsystem.Thisstudyprovidesrobustevidencethatthedensityoftumourinfiltratinglymphocytesdemonstratesahighprognosticsignificanceinoralsquamouscellcarcinoma.

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Locally advanced breast cancer: Tumor-infiltrating lymphocytes as a predictive factor of response to neoadjuvant chemotherapy

Cited by 29 publications

References 18 publications

The Immunology of Hormone Receptor Positive Breast Cancer

The Immunology of Hormone Receptor Positive Breast Cancer

Predictive Value of Tumor Infiltrating Lymphocytes in Neoadjuvant Chemotherapy Treated Breast Cancer: A Meta-Analysis of 8052 Patients

The prognostic significance of tumour infiltrating lymphocytes in oral squamous cell carcinoma

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