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      Call for Papers: Beyond Biology: The Crucial Role of Sex and Gender in Oncology

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      About Oncology Research and Treatment: 2.4 Impact Factor I 3.3 CiteScore I 0.495 Scimago Journal & Country Rank (SJR)

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      Tumor-Infiltrating Lymphocytes: A Promising Biomarker in Breast Cancer

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          Abstract

          There is clear evidence that the immune system plays an essential role in tumor defense. By determining tumor-infiltrating lymphocytes (TILs), the individual immunological response becomes more apparent and measurable. In breast cancer, high levels of TILs are associated with a more favorable clinical course. In this review, we describe how TILs are determined with emphasis on daily routine diagnostics. We further discuss their impact as a prognostic and predictive biomarker in the neoadjuvant and adjuvant therapy setting as well as in residual disease. We also discuss their potential future implications on further stratifying prognostic subgroups of breast cancer, thereby possibly influencing future therapy considerations.

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          Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer.

          Carsten Denkert, Sibylle Loibl, Aurelia Noske … (2010)
          PURPOSE Preclinical data suggest a contribution of the immune system to chemotherapy response. In this study, we investigated the prespecified hypothesis that the presence of a lymphocytic infiltrate in cancer tissue predicts the response to neoadjuvant chemotherapy. METHODS We investigated intratumoral and stromal lymphocytes in a total of 1,058 pretherapeutic breast cancer core biopsies from two neoadjuvant anthracycline/taxane-based studies (GeparDuo, n = 218, training cohort; and GeparTrio, n = 840, validation cohort). Molecular parameters of lymphocyte recruitment and activation were evaluated by kinetic polymerase chain reaction in 134 formalin-fixed, paraffin-embedded tumor samples. Results In a multivariate regression analysis including all known predictive clinicopathologic factors, the percentage of intratumoral lymphocytes was a significant independent parameter for pathologic complete response (pCR) in both cohorts (training cohort: P = .012; validation cohort: P = .001). Lymphocyte-predominant breast cancer responded, with pCR rates of 42% (training cohort) and 40% (validation cohort). In contrast, those tumors without any infiltrating lymphocytes had pCR rates of 3% (training cohort) and 7% (validation cohort). The expression of inflammatory marker genes and proteins was linked to the histopathologic infiltrate, and logistic regression showed a significant association of the T-cell-related markers CD3D and CXCL9 with pCR. CONCLUSION The presence of tumor-associated lymphocytes in breast cancer is a new independent predictor of response to anthracycline/taxane neoadjuvant chemotherapy and provides useful information for oncologists to identify a subgroup of patients with a high benefit from this type of chemotherapy.
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            Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199.

            Sylvia Adams, Robert J. Gray, Sandra Demaria … (2014)
            Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG). Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified. The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS. In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.
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              Immunological aspects of cancer chemotherapy.

              Laurence Zitvogel, Lionel Apetoh, Francois Ghiringhelli … (2008)
              Accumulating evidence indicates that the innate and adaptive immune systems make a crucial contribution to the antitumour effects of conventional chemotherapy-based and radiotherapy-based cancer treatments. Moreover, the molecular and cellular bases of the immunogenicity of cell death that is induced by cytotoxic agents are being progressively unravelled, challenging the guidelines that currently govern the development of anticancer drugs. Here, we review the immunological aspects of conventional cancer treatments and propose that future successes in the fight against cancer will rely on the development and clinical application of combined chemo- and immunotherapies.
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                Author and article information

                Journal
                Journal ID (publisher-id): BRC
                Journal ID (pmc): BRC
                Journal ID (doi): 10.1159/issn.1661-3791
                Title: Breast Care
                Publisher: S. Karger AG
                ISSN (Print): 1661-3791
                ISSN (Electronic): 1661-3805
                Publication date Subscription-year: 2016
                Publication date (Print): April 2016
                Publication date (Electronic): 26 April 2016
                Volume: 11
                Issue: 2
                Pages: 96-100
                Affiliations
                a Institut für Pathologie, Charité Universitätsmedizin, Berlin, Germany; b German Breast Group (GBG) c/o Forschungs GmbH, Neu-Isenburg, Germany; c Sana Klinikum Offenbach, Offenbach, Germany; d German Cancer Consortium (DKTK), Berlin, Germany
                Article
                Publisher ID: 444357 Pmcid ID: PMC4881255 Other ID: Breast Care 2016;11:96-100
                DOI: 10.1159/000444357
                PMC ID: PMC4881255
                PubMed ID: 27239170
                SO-VID: 2c3842d7-97f6-49a9-beb7-3571fb3281a7
                Copyright © © 2016 S. Karger GmbH, Freiburg
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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                Page count
                Figures: 1, Tables: 1, References: 40, Pages: 5
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Oncology & Radiotherapy,Pathology,Surgery,Obstetrics & Gynecology,Pharmacology & Pharmaceutical medicine,Hematology
                Keywords: Pathological complete response,Breast cancer,Neoadjuvant,Tumor-infiltrating lymphocytes,Adjuvant
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy, Pathology, Surgery, Obstetrics & Gynecology, Pharmacology & Pharmaceutical medicine, Hematology
                Keywords: Pathological complete response, Breast cancer, Neoadjuvant, Tumor-infiltrating lymphocytes, Adjuvant

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