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      Triple negative breast cancer: Pitfalls and progress

      review-article
      1 , 2 , 2 ,
      NPJ Breast Cancer
      Nature Publishing Group UK
      Breast cancer, Breast cancer

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          Abstract

          Triple negative breast cancer (TNBC) is characterized by the lack of estrogen and progesterone receptor expression and lacks HER2 overexpression or gene amplification. It accounts for 10–15% of incident breast cancers and carries the worst prognosis. TNBC is overrepresented among Black and pre-menopausal women and is associated with significant psychological and treatment-related burdens, including financial toxicity. Like other breast cancers, TNBC is biologically heterogeneous, leading to diverse clinical and epidemiological behaviors, however, unlike the other clinical subtypes, in TNBC we still lack tumor-specific targeted therapy. Early TNBC outcomes have improved due to the intensification of therapies, including improvements in polychemotherapy and the addition of immunotherapy. Future efforts are needed to identify targetable aberrations for specific drug therapy, prevent immune evasion, and increase social-economic support. Given that the name TNBC illustrates its lack of specifically targeted and effective therapy, we look forward to being able to retire the name in favor of a group of targetable entities within what is now called “TNBC”.

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          Most cited references96

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Comprehensive molecular portraits of human breast tumors

            Summary We analyzed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, mRNA arrays, microRNA sequencing and reverse phase protein arrays. Our ability to integrate information across platforms provided key insights into previously-defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at > 10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the Luminal A subtype. We identified two novel protein expression-defined subgroups, possibly contributed by stromal/microenvironmental elements, and integrated analyses identified specific signaling pathways dominant in each molecular subtype including a HER2/p-HER2/HER1/p-HER1 signature within the HER2-Enriched expression subtype. Comparison of Basal-like breast tumors with high-grade Serous Ovarian tumors showed many molecular commonalities, suggesting a related etiology and similar therapeutic opportunities. The biologic finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biologic subtypes of breast cancer.
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              Oncology meets immunology: the cancer-immunity cycle.

              The genetic and cellular alterations that define cancer provide the immune system with the means to generate T cell responses that recognize and eradicate cancer cells. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which manages the delicate balance between the recognition of nonself and the prevention of autoimmunity. Identification of cancer cell T cell inhibitory signals, including PD-L1, has prompted the development of a new class of cancer immunotherapy that specifically hinders immune effector inhibition, reinvigorating and potentially expanding preexisting anticancer immune responses. The presence of suppressive factors in the tumor microenvironment may explain the limited activity observed with previous immune-based therapies and why these therapies may be more effective in combination with agents that target other steps of the cycle. Emerging clinical data suggest that cancer immunotherapy is likely to become a key part of the clinical management of cancer. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                lisa_carey@med.unc.edu
                Journal
                NPJ Breast Cancer
                NPJ Breast Cancer
                NPJ Breast Cancer
                Nature Publishing Group UK (London )
                2374-4677
                20 August 2022
                20 August 2022
                2022
                : 8
                : 95
                Affiliations
                [1 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Department of Oncology and Hematology, , University of Milano, ; Milan, Italy
                [2 ]GRID grid.10698.36, ISNI 0000000122483208, Lineberger Comprehensive Cancer Center, , University of North Carolina at Chapel Hill, ; Chapel Hill, NC USA
                Author information
                http://orcid.org/0000-0002-2687-6436
                http://orcid.org/0000-0003-2388-4649
                Article
                468
                10.1038/s41523-022-00468-0
                9392735
                35987766
                a7c8830c-44e7-43e9-a514-69c2f2210847
                © The Author(s) 2022

                Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 1 March 2022
                : 28 July 2022
                Funding
                Funded by: Ermenegildo Zegna scholarship
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2022

                breast cancer
                breast cancer

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