A novel approach to triple-negative breast cancer molecular classification reveals a luminal immune-positive subgroup with good prognoses

Aim: To develop an approach to characterize and classify triple-negative breast cancer (TNBC) tumors based upon their essential amino acid (EAA) metabolic activity. Methods: We performed bioinformatic analyses of genomic, transcriptomic and clinical data in an integrated cohort of 740 TNBC patients from public databases. Results: Based on EAA metabolism-related gene expression patterns, two TNBC subtypes were identified with distinct prognoses and genomic alterations. Patients exhibiting an upregulated EAA metabolism phenotype were more prone to chemoresistance but also expressed higher levels of immune checkpoint genes and may be better candidates for immune checkpoint inhibitor therapy. Conclusion: Metabolic classification based upon EAA profiles offers a novel biological insight into previously established TNBC subtypes and advances current understanding of TNBC’s metabolic heterogeneity.

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Latest changes in the molecular classification of breast cancer and triple negative breast cancer

Varna Medical Forum ◽

10.14748/vmf.v8i2.6046 ◽

2019 ◽

Vol 8 (2) ◽

pp. 80

Author(s):

Vassilena Tsvetkova

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Molecular Classification

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Molecular Classification and Future Therapeutic Challenges of Triple-negative Breast Cancer

In Vivo ◽

10.21873/invivo.11965 ◽

2020 ◽

Vol 34 (4) ◽

pp. 1715-1727

Author(s):

NIKOLAOS GARMPIS ◽

CHRISTOS DAMASKOS ◽

ANNA GARMPI ◽

KONSTANTINOS NIKOLETTOS ◽

DIMITRIOS DIMITROULIS ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Molecular Classification

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Molecular classification with NanoString nCounter system in triple-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e23198 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e23198-e23198

Author(s):

Sung Gwe Ahn ◽

Seung Joon Kim ◽

Hak Woo Lee ◽

Hyo Jeong Yoon ◽

Chungyeul Kim ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Drug Response ◽

Triple Negative ◽

Molecular Classification ◽

Severance Hospital ◽

Brca1 Promoter Methylation ◽

Pearson's R ◽

Pearson’S R

e23198 Background: Previous studies have shown that several distinct subtypes identified by gene expression profiling (GEP) consisted of triple-negative breast cancer (TNBC). Compared with the subtypes defined by GEP, we developed molecular classification with NanoString nCounter system in TNBC. Methods: GEP was conducted on 188 FFPE containing chemotherapy-naïve TNBC tumors collected at Gangnam Severance Hospital. To select core genes for classification, other 120 samples from public GEP database were used. Correlation between nCounter system and GEP using identical RNA was done. In a part of tumors, BRCA1 methylation, homologous recombination deficiency (HRD) assay, and drug response assay with ATP was comprehensively assessed. Results: To classify TNBC into 4 major subtypes (Basal-like: BL, Luminal androgen receptor: LAR, Mesenchymal: M, and Immune-modulatory: IM) according to the Vanderbilt classification, we selected 110 genes in 220 samples with GEP (100 from Gangnam Severance Hospital and 120 from public database). In other 88 samples, the classification with the 110 genes were validated. In 149 tumors excluding UNS subtype by the Vanderbilt, a correlation between 110 genes-classification and the Vanderbilt system was 74.4% (111 of 149, Pearson’s R = 0.726). In 180 tumors with GEP and nCounter assay, a correlation between them was 85.0% (153 of 180, Pearson’s R = 0.827). Compared with tumors of the IM type by 110-genes, the recurrence-free survival was significantly reduced in tumors of the non-IM type by 110-genes ( P= 0.049). In cases with BRCA1 methylation test (n = 147), a significant higher rate of BRCA1 promoter methylation was found in BL type by nCounter system (BL: 41.0% vs. non-BL: 19.4%). In cases with HRD test, a significant lower rate of HRD was found in nCounter-identified LAR type (LAR: 0% vs. non-LAR: 79.3%). In patients with in vitro drug response assay with cisplatin (n = 36), tumors with nCounter-BL had a significant higher responsiveness than tumors with others ( P= 0.028). Conclusions: Our work shows the feasibility of molecular classification with nCounter system in TNBC. Future study warrants the clinical utility of this classification to guide the subtype-specific therapy in patients with TNBC.

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Pseudopterosin Inhibits Proliferation and 3D Invasion in Triple Negative Breast Cancer by Agonizing Glucocorticoid Receptor Alpha

10.20944/preprints201807.0224.v2 ◽

2018 ◽

Author(s):

Julia Sperlich ◽

Nicole Teusch

Keyword(s):

Breast Cancer ◽

Glucocorticoid Receptor ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Mononuclear Cells ◽

Biological Activities ◽

Tumor Spheroids ◽

Peripheral Blood Mononuclear ◽

Surrounding Matrix ◽

Novel Approach

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.

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Abstract 5592: Molecular classification of triple negative breast cancer via RNA-sequencing data

10.1158/1538-7445.am2014-5592 ◽

2014 ◽

Author(s):

Kevin J. Thompson ◽

Xiaojia Tang ◽

Zhifu Sun ◽

Jason P. Sinnwell ◽

Hugues Sicotte ◽

...

Keyword(s):

Breast Cancer ◽

Rna Sequencing ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Molecular Classification ◽

Sequencing Data

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A novel approach for targeted elimination of CSPG4-positive triple-negative breast cancer cells using a MAP tau-based fusion protein

International Journal of Cancer ◽

10.1002/ijc.30119 ◽

2016 ◽

Vol 139 (4) ◽

pp. 916-927 ◽

Cited By ~ 18

Author(s):

Manal Amoury ◽

Radoslav Mladenov ◽

Thomas Nachreiner ◽

Anh-Tuan Pham ◽

Dmitrij Hristodorov ◽

...

Keyword(s):

Breast Cancer ◽

Fusion Protein ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Novel Approach

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Ultra-sensitive Nanoprobe Modified with Tumor Cell Membrane for UCL/MRI/PET Multimodality Precise Imaging of Triple-Negative Breast Cancer

Nano-Micro Letters ◽

10.1007/s40820-020-0396-4 ◽

2020 ◽

Vol 12 (1) ◽

Cited By ~ 4

Author(s):

Hanyi Fang ◽

Mengting Li ◽

Qingyao Liu ◽

Yongkang Gai ◽

Lujie Yuan ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Imaging ◽

Cell Membrane ◽

Cancer Cell ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Molecular Classification ◽

Upconversion Nanoparticles ◽

Targeting Ability

AbstractTriple-negative breast cancer (TNBC) is a subtype of breast cancer in which the estrogen receptor and progesterone receptor are not expressed, and human epidermal growth factor receptor 2 is not amplified or overexpressed either, which make the clinical diagnosis and treatment very challenging. Molecular imaging can provide an effective way to diagnose TNBC. Upconversion nanoparticles (UCNPs), are a promising new generation of molecular imaging probes. However, UCNPs still need to be improved for tumor-targeting ability and biocompatibility. This study describes a novel probe based on cancer cell membrane-coated upconversion nanoparticles (CCm-UCNPs), owing to the low immunogenicity and homologous-targeting ability of cancer cell membranes, and modified multifunctional UCNPs. This probe exhibits excellent performance in breast cancer molecular classification and TNBC diagnosis through UCL/MRI/PET tri-modality imaging in vivo. By using this probe, MDA-MB-231 was successfully differentiated between MCF-7 tumor models in vivo. Based on the tumor imaging and molecular classification results, the probe is also expected to be modified for drug delivery in the future, contributing to the treatment of TNBC. The combination of nanoparticles with biomimetic cell membranes has the potential for multiple clinical applications.

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