Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

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Abstract

Triple-negative breast cancer (TNBC) cells are deficient in estrogen, progesterone and ERBB2 receptor expression, presenting a particularly challenging therapeutic target due to their highly invasive nature and relatively low response to therapeutics. There is an absence of specific treatment strategies for this tumor subgroup, and hence TNBC is managed with conventional therapeutics, often leading to systemic relapse. In terms of histology and transcription profile these cancers have similarities to BRCA-1-linked breast cancers, and it is hypothesized that BRCA1 pathway is non-functional in this type of breast cancer. In this review article, we discuss the different receptors expressed by TNBC as well as the diversity of different signaling pathways targeted by TNBC therapeutics, for example, Notch, Hedgehog, Wnt/b-Catenin as well as TGF-beta signaling pathways. Additionally, many epidermal growth factor receptor (EGFR), poly (ADP-ribose) polymerase (PARP) and mammalian target of rapamycin (mTOR) inhibitors effectively inhibit the TNBCs, but they face challenges of either resistance to drugs or relapse. The resistance of TNBC to conventional therapeutic agents has helped in the advancement of advanced TNBC therapeutic approaches including hyperthermia, photodynamic therapy, as well as nanomedicine-based targeted therapeutics of drugs, miRNA, siRNA, and aptamers, which will also be discussed. Artificial intelligence is another tool that is presented to enhance the diagnosis of TNBC.

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The blockade of immune checkpoints in cancer immunotherapy.

Drew M Pardoll (2012)

Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.

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Breast cancer molecular subtypes respond differently to preoperative chemotherapy.

Roman Rouzier, Charles Perou, W Symmans … (2005)

Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported "breast intrinsic" gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor-negative subtypes. The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.

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Incidence and Mortality and Epidemiology of Breast Cancer in the World.

Hamid Salehiniya, Zahra pournamdar, Mahshid Ghoncheh (2016)

Breast cancer is the most common malignancy in women around the world. Information on the incidence and mortality of breast cancer is essential for planning health measures. This study aimed to investigate the incidence and mortality of breast cancer in the world using age-specific incidence and mortality rates for the year 2012 acquired from the global cancer project (GLOBOCAN 2012) as well as data about incidence and mortality of the cancer based on national reports. It was estimated that 1,671,149 new cases of breast cancer were identified and 521,907 cases of deaths due to breast cancer occurred in the world in 2012. According to GLOBOCAN, it is the most common cancer in women, accounting for 25.1% of all cancers. Breast cancer incidence in developed countries is higher, while relative mortality is greatest in less developed countries. Education of women is suggested in all countries for early detection and treatment. Plans for the control and prevention of this cancer must be a high priority for health policy makers; also, it is necessary to increase awareness of risk factors and early detection in less developed countries.

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Journal

Journal ID (nlm-ta): Int J Environ Res Public Health

Journal ID (iso-abbrev): Int J Environ Res Public Health

Journal ID (publisher-id): ijerph

Title: International Journal of Environmental Research and Public Health

Publisher: MDPI

ISSN (Print): 1661-7827

ISSN (Electronic): 1660-4601

Publication date (Electronic): 20 March 2020

Publication date (Print): March 2020

Volume: 17

Issue: 6

Electronic Location Identifier: 2078

Affiliations

[1 ]Department of Nanoscience and Nanotechnology, CINVESTAV, Zacatenco, Avenida Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico

[2 ]Centro de Investigación y Desarrollo Tecnológico en Electroquímica (CIDETEQ), Parque Tecnológico Querétaro s/n, Sanfandila. Pedro Escobedo, Querétaro 76703, Mexico; larriaga@ 123456cideteq.mx

[3 ]Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, Av. Epigmenio González No. 500, Fracc. San Pablo, Queretaro 76130, Mexico; asharma@ 123456tec.mx

[4 ]Department of Cell Biology, CINVESTAV, Zacatenco, Avenida Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico

[5 ]Department of Chemistry, University of Massachusetts, 710 North Pleasant Street, Amherst, MA 01003, USA; rotello@ 123456umass.edu

[6 ]Department of Genetics and Molecular Biology, CINVESTAV, Zacatenco, Avenida Instituto Politécnico Nacional 2508, Mexico City 07360, Mexico

Author notes

[* ]Correspondence: mauricio.medina@ 123456cinvestav.mx (M.A.M.); goza@ 123456cideteq.mx (G.O.); jtapia@ 123456cinvestav.mx (J.T.R.)

Author information

Mauricio A. Medina https://orcid.org/0000-0002-5068-7678

Goldie Oza https://orcid.org/0000-0003-1051-0795

Ashutosh Sharma https://orcid.org/0000-0002-9000-1378

Vincent M. Rotello https://orcid.org/0000-0002-5184-5439

Jose Tapia Ramirez https://orcid.org/0000-0002-4641-7181

Article

Publisher ID: ijerph-17-02078

DOI: 10.3390/ijerph17062078

PMC ID: 7143295

PubMed ID: 32245065

SO-VID: a1509ef2-44b8-45df-aba6-6cda5a487753

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

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Most cited references 175

The blockade of immune checkpoints in cancer immunotherapy.

Breast cancer molecular subtypes respond differently to preoperative chemotherapy.

Incidence and Mortality and Epidemiology of Breast Cancer in the World.

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