Triple negative breast cancer: Deciphering the biology and heterogeneity

Uscanga‑Perales, Grecia I.; Santuario‐Facio, Sandra K.; Ortı́z-López, Rocio

doi:10.1016/j.rmu.2016.05.007

Cited by 30 publications

(28 citation statements)

References 72 publications

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“…Whilst the morphology type showed there was no statistically significant difference observed, the molecular subtypes (HER2 enriched and TNBC) subjects were at increased risk of fiveyear mortality. The latter is consistent with literature finding [13][14][15][16][17][18][19][20] . The study could not do full SHR's for the ER and PR for the various ethnicity groups due to small cell counts, so our outcome is preliminary here.…”

Section: Prognostic Factorssupporting

confidence: 93%

Understanding risk factors in grade 3 breast cancer in NZ

Meharry

Ramsaroop²,

Borotkanics

et al. 2020

Preprint

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Background Breast cancer is the most common cancer in New Zealand women, accounting for approximately 3000 new registrations per year, affecting one in nine women and resulting in more than 600 deaths annually. This study analysed data of patients selected with prognostic factor of Nottingham grade 3 tumours over a specified five- year period. These represent a heterogeneous group of cancers with variable survival rates. Method All women diagnosed with Nottingham grade 3 invasive breast cancer between 1 st January 2011 to 31 st December 2015, from four Breast Cancer Registries in New Zealand (Auckland, Waikato, Christchurch, and Wellington) were studied. Results Applying Fine-Gray analyses, the study of 2,493 women found that subjects in the older age group (>70 years) had a higher five-year mortality risk (SHR: 1.74 to 2.25, p: 0.053 to <0.001). Analysis of hormonal receptors showed that tumours with hormonal profile ER-positive, PR negative and ER-negative, PR negative subjects were at increased mortality risk (SHR: 3.56, p: <0.001) and (SHR: 2.67, p: <0.001) respectively. Molecular subtypes TNBC and Luminal B subjects were at increased risk of five-year mortality (SHR: 3.01 and 3.35 respectively, both p: <0.001). HER2 enriched subjects, were at elevated risk (SHR: 1.66, p: 0.11). Women identifying as NZ European ethnicity were at elevated risk of mortality overall (SHR: 1.70, p: 0.11), and they presented with the highest CIF across ethnicities. The NZ Europeans represented the largest proportion of HER2 enriched and TNBC subjects; however, Pacific Islanders experienced the highest HER2 CIF. Conclusion The survival rates for grade 3 breast cancer vary across the selected prognostic factors and ethnicity. Although grade 3 breast cancer is considered as high grade heterogeneous cancer, this study showed that not every patient has a poor outcome. NZ Europeans are worst affected followed by Pacific Islanders. Biology of the cancer and ethnicity needs to be looked at as a possible factor associated with this disease for survival differences. The results of this study make an initial contribution to the understanding of high-grade malignancy and other prognostic factors must be included in order to get a better understanding of survival differences.

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Section: Prognostic Factorssupporting

confidence: 93%

Understanding risk factors in grade 3 breast cancer in NZ

Meharry

Ramsaroop²,

Borotkanics

et al. 2020

Preprint

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“…Loss of BUB1 mitotic checkpoint serine/threonine kinase (BUB1) could reduce cancer stem cell potential of breast cancer cell line [ 39 ]. Minichromosome maintenance 10 replication initiation factors (MCM10) were recognized as biomarker for identification of subtype TNBC [ 40 ]. Above all, these genes either promote or inhibit the progression of TNBC that the complex interaction between genes need to be explored.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Pathways in Triple-Negative Breast Cancer by Integrated Bioinformatics Analysis

Dong

Pan

et al. 2018

BioMed Research International

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Purpose Triple-negative breast cancer refers to breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (Her2). This study aimed to identify the key pathways and genes and find the potential initiation and progression mechanism of triple-negative breast cancer (TNBC). Methods We downloaded the gene expression profiles of GSE76275 from Gene Expression Omnibus (GEO) datasets. This microarray Super-Series sets are composed of gene expression data from 265 samples which included 67 non-TNBC and 198 TNBC. Next, all the differentially expressed genes (DEGs) with p<0.01 and fold change ≥1.5 or ≤-1.5 were identified. Result 56 upregulated and 151 downregulated genes were listed and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis was performed. These significantly changed genes were mainly involved in the biological process termed prostate gland morphogenesis, inner ear morphogenesis, cell maturation, digestive tract morphogenesis, autonomic nervous system development, monovalent inorganic anion homeostasis, neural crest cell development, regulation of dendrite extension and glial cell proliferation, immune system process termed T cell differentiation, regulation of immune response, and macrophage activation. Genes are mainly involved in the KEGG pathway termed Oocyte meiosis. All DEGs underwent survival analysis using datasets from The Cancer Genome Atlas (TCGA) integrated by cBioPortal, of which amplification of SRY-related HMG-box 8 (SOX8), androgen receptor (AR), and Chromosome 9 Open Reading Frame 152 (C9orf152) were significantly negative while Nik Related Kinase (NRK) and RAS oncogene family 30 (RAB30) were positively correlated to the life expectancy (p<0.05). Conclusions In conclusion, these pathways and genes identified could help understanding the mechanism of development of TNBC. Besides, SOX8, AR, C9orf152, NRK and RAB30, and other key genes and pathways might be promising targets for the TNBC treatment.

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“…No targeted treatment exists for this particular class, and chemotherapy and surgery remain the best therapeutic options. However, in the case of resistance or lack of response to treatment, options are very limited …”

Section: Hormone Receptorsmentioning

confidence: 99%

The aryl hydrocarbon receptor (AhR) as a breast cancer drug target

Baker

Sakoff

McCluskey

2019

Medicinal Research Reviews

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Breast cancer is the most common cancer in women, with more than 1.7 million diagnoses worldwide per annum. Metastatic breast cancer remains incurable, and the presence of triplenegative phenotypes makes targeted treatment impossible. The aryl hydrocarbon receptor (AhR), most commonly associated with the metabolism of xenobiotic ligands, has emerged as a promising biological target for the treatment of this deadly disease. Ligands for the AhR can be classed as exogenous or endogenous and may have agonistic or antagonistic activity. It has been well reported that agonistic ligands may have potent and selective growth inhibition activity in a number of oncogenic cell lines, and one (aminoflavone) has progressed to phase I clinical trials for breast cancer sufferers. In this study, we examine the current state of the literature in this area and elucidate the promising advances that are being made in hijacking the cytosolic-to-nuclear pathway of the AhR for the possible future treatment of breast cancer. K E Y W O R D S aryl hydrocarbon receptor, breast cancer, cancer drugs Abbreviations: 3MC, 3-methylcholanthrene; AF, aminoflavone; AF-1, activation function domain 1; AF-2, activation function domain 2; AhR, aryl hydrocarbon receptor; AhRR, aryl hydrocarbon receptor repressor; AIP, aryl hydrocarbon receptor-interacting protein; ANI-7, (Z)-2-(3,4-dichlorophenyl)-3-(1H-pyrrol-2-yl)acrylonitrile; ARNT, aryl hydrocarbon receptor nuclear translocator; BaP, benzo[a]pyrene; BE, botanical estrogen; bHLH, basic helixloop-helix; βNF, β-naphthoflavone; BRCA1, breast cancer susceptibility gene 1; BRCA2, breast cancer susceptibility gene 2; DNF, dinaphtho[1,2-b;1′2'-d] furan; ER, estrogen receptor; FDA, US Food and Drug Administration; FICZ, 6-formylindolo[3,2-b]carbazole; HAHs, halogenated aromatic hydrocarbons; HER-2, human epidermal growth factor receptor 2; HR, hormone receptor; Hsp90, heat shock protein 90; ITE, 2-(1′H-indole-3′-carbonyl)-thiazole-4carboxylic acid ester; LBD, ligand-binding domain; NLS, nuclear localization sequences; NSAID, nonsteroidal anti-inflammatory drug; p23, prostaglandin E synthase 3; PAHs, polycyclic aromatic hydrocarbons; PAS, period-aryl hydrocarbon receptor nuclear translocator-single minded; PAS-A, period-aryl hydrocarbon receptor nuclear translocator-single minded domain A; PAS-B, period-aryl hydrocarbon receptor nuclear translocator-single minded domain B; PCB, 3,3′,4,4′,5-pentachlorobiphenyl; PPI, proton pump inhibitor; PR, progesterone receptor; PR-A, progesterone receptor form A; PR-B, progesterone receptor form B; PR-C, progesterone receptor form C; ROS, reductive oxidative species; SERMs, selective estrogen receptor modulators; SULT1A1, sulfotransferase 1A1; TAD, transactivation domain; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDF, 2,3,7,8-tetrachlorodibenzofuran; TNBC, triplenegative breast cancer; Tregs, regulatory T cells; XAP-2, hepatitis B virus X-associated protein 2; XRE, xenobiotic response element. | BREAST CANCER BACKGROUNDBreast cancer is the most common cancer in women. Of...

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Triple negative breast cancer: Deciphering the biology and heterogeneity

Cited by 30 publications

References 72 publications

Understanding risk factors in grade 3 breast cancer in NZ

Understanding risk factors in grade 3 breast cancer in NZ

Identification of Key Genes and Pathways in Triple-Negative Breast Cancer by Integrated Bioinformatics Analysis

The aryl hydrocarbon receptor (AhR) as a breast cancer drug target

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