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      Invasive lobular carcinoma of the breast: the increasing importance of this special subtype

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          Abstract

          Invasive lobular carcinoma (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast cancer cases. ILCs are noted for their lack of E-cadherin function, which underpins their characteristic discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, tumours are luminal in molecular subtype, being oestrogen and progesterone receptor positive, and HER2 negative. Since last reviewing the lobular literature (McCart Reed et al., Breast Cancer Res 17:12, 2015), there has been a considerable increase in research output focused on this tumour type, including studies into the pathology and management of disease, a high-resolution definition of the genomic landscape of tumours as well as the evolution of several potential therapeutic avenues. There abounds a huge amount of new data, which we will review herein.

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          The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014.

          The morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is gaining momentum as evidence strengthens for the clinical relevance of this immunological biomarker. Accumulating evidence suggests that the extent of lymphocytic infiltration in tumor tissue can be assessed as a major parameter by evaluation of hematoxylin and eosin (H&E)-stained tumor sections. TILs have been shown to provide prognostic and potentially predictive value, particularly in triple-negative and human epidermal growth factor receptor 2-overexpressing BC. A standardized methodology for evaluating TILs is now needed as a prerequisite for integrating this parameter in standard histopathological practice, in a research setting as well as in clinical trials. This article reviews current data on the clinical validity and utility of TILs in BC in an effort to foster better knowledge and insight in this rapidly evolving field, and to develop a standardized methodology for visual assessment on H&E sections, acknowledging the future potential of molecular/multiplexed approaches. The methodology provided is sufficiently detailed to offer a uniformly applied, pragmatic starting point and improve consistency and reproducibility in the measurement of TILs for future studies. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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            Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer

            The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score.
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              Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

              Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.
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                Author and article information

                Contributors
                amy.reed@uq.edu.au
                Journal
                Breast Cancer Res
                Breast Cancer Res
                Breast Cancer Research : BCR
                BioMed Central (London )
                1465-5411
                1465-542X
                7 January 2021
                7 January 2021
                2021
                : 23
                : 6
                Affiliations
                [1 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, UQ Centre for Clinical Research, , The University of Queensland, ; Herston, Brisbane, Australia
                [2 ]GRID grid.1049.c, ISNI 0000 0001 2294 1395, QIMR Berghofer Medical Research Institute, ; Herston, Brisbane, Australia
                [3 ]GRID grid.508265.c, ISNI 0000 0004 0500 8378, Department of Histopathology, , Sullivan Nicolaides Pathology, ; Bowen Hills, Brisbane, Australia
                [4 ]GRID grid.416100.2, ISNI 0000 0001 0688 4634, Pathology Queensland, , Royal Brisbane and Women’s Hospital, ; Herston, Brisbane, Australia
                Article
                1384
                10.1186/s13058-020-01384-6
                7792208
                33413533
                935d0b37-e6ff-457b-bb04-a323cf875d47
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 10 September 2020
                : 15 December 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: APP1159902
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                ilc,lobular,lobular breast cancer,genomics,pathology,lcis,lobular neoplasia
                Oncology & Radiotherapy
                ilc, lobular, lobular breast cancer, genomics, pathology, lcis, lobular neoplasia

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