Abstract P3-07-27: Distinct biomarker features in triple-negative breast cancer metastases to the brain, liver and bone

Following lung cancer, breast cancer is the second most common metastatic tumor to the brain, of which triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2+ (HER2+) breast cancer are the most common subtypes. TNBC does not have standard immunoprofiles and can be difficult to distinguish from other metastases. A tissue microarray was created from 47 patients with breast cancer metastases to the brain and 12 paired breast primaries. Of 47 breast cancer metastases, 24 were HER2+, 14 were TNBC, and 9 were luminal. Forty-five were cytokeratin 7 (CK7) positive, 36 were GATA-binding protein 3 (GATA3) positive, 7 were Sry-related HMg-Box gene 10 (SOX-10) positive, 20 were mammaglobin positive, and 19 were gross cystic disease fluid protein 15 positive. At least one of the CK7, GATA3, or SOX-10 was positive in all TNBC metastases. A panel of CK7, GATA3, and SOX-10 is complementary in the diagnosis of breast cancer brain metastasis. SOX-10 appears to be a specific but not particularly sensitive marker in this context.

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Abstract P1-07-05: Triple negative breast cancer metastases: Protein signal transduction networks within the tumor-stromal microenvironment complement genomic analysis and stratify local versus distant metastasis

10.1158/1538-7445.sabcs14-p1-07-05 ◽

2015 ◽

Author(s):

Virginia Espina ◽

Maren K Levin ◽

John D Carpten ◽

David W Craig ◽

Daniel Von Hoff ◽

...

Keyword(s):

Breast Cancer ◽

Signal Transduction ◽

Triple Negative Breast Cancer ◽

Distant Metastasis ◽

Triple Negative ◽

Genomic Analysis ◽

Breast Cancer Metastases ◽

Stromal Microenvironment ◽

Cancer Metastases ◽

Signal Transduction Networks

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BSCI-05. HOW MICROGLIA, BRAIN RESIDENT MYELOID CELLS, RESPOND TO BREAST CANCER METASTASIS INTO THE BRAIN?

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.004 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i2-i2

Author(s):

Kamil Wojnicki ◽

Agata Kochalska ◽

Anna Gieryng ◽

Tomasz Czernicki ◽

Ewa Matyja ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Human Breast Cancer ◽

Triple Negative ◽

Metastatic Cancer ◽

Human Breast ◽

Breast Cancer Metastases ◽

Cancer Metastases ◽

The Brain ◽

Metastatic Cancer Cells

Abstract Brain metastasis from different cancers, including lung, breast, melanoma, colorectal or renal cell carcinoma is relatively common and its frequency increases with a prolonged survival of cancer patients. New anti-cancer therapies frequently fail to reduce metastatic burden. While the important role of tumor-associated macrophages as pro-tumorigenic cells facilitating tissue remodeling, invasion and metastasis is well documented, much less is known about the immune microenvironment of brain metastases and potential mechanisms that mediate interactions of cancer cells with brain immune cells - microglia. Triple-negative breast cancer metastases to the brain were discovered in 46% of patients. We evaluated the abundance and morphology of microglia on sections from breast cancer metastases using immunohistochemistry. We found that microglia cells are activated, surround the breast tumor cells and do not infiltrate the solid tumor. Searching for a potential attractant of microglia, we determined osteopontin levels in six human breast cancer cell lines and found upregulation of osteopontin in transformed cells, with the highest level in the triple-negative MDA-MB-231 cells. MDA-MB-231 cells activated primary murine microglia cultures when co-cultured. Invasion of MDA-MB-231 cells in co-cultures with murine immortalized BV2 microglial cells and human SV40 immortalized microglia was increased, as demonstrated using Matrigel Invasion Assay. Using immunofluorescence we detected osteopontin in cancer cells in human breast cancer metastases. Moreover, we found that minocycline, a clinically used antibiotic, reduces the osteopontin production in human breast cancer cells and the most sensitive cells were MDA-MB-231 cells. Our study shows that metastatic cancer cells may employ microglia to facilitate extravasation and colonization of brain parenchyma. We postulate that osteopontin mediates interactions between microglia and metastatic cancer cells and minocycline may interfere with those interactions. Funding: TEAM TECH CORE FACILITY FNP: Development of comprehensive diagnostics and personalized therapy in neuro-oncology

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Abstract 2035: Knockdown of TGFβ-activated ATF4 inhibits triple negative breast cancer metastases independently of cellular stress

10.1158/1538-7445.am2018-2035 ◽

2018 ◽

Author(s):

Jenny C. Chang ◽

Alberto Ramirez ◽

Maria P. Molina ◽

Francisca E. Cara ◽

Wei Qian ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cellular Stress ◽

Breast Cancer Metastases ◽

Cancer Metastases

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Targeted imaging and inhibition of triple-negative breast cancer metastases by a PDGFRβ aptamer

Theranostics ◽

10.7150/thno.27798 ◽

2018 ◽

Vol 8 (18) ◽

pp. 5178-5199 ◽

Cited By ~ 12

Author(s):

Simona Camorani ◽

Billy Samuel Hill ◽

Francesca Collina ◽

Sara Gargiulo ◽

Maria Napolitano ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Targeted Imaging ◽

Breast Cancer Metastases ◽

Cancer Metastases

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Progesterone suppresses triple-negative breast cancer growth and metastasis to the brain via membrane progesterone receptor α

International Journal of Molecular Medicine ◽

10.3892/ijmm.2017.3060 ◽

2017 ◽

Vol 40 (3) ◽

pp. 755-761 ◽

Cited By ~ 9

Author(s):

Li Zhou ◽

Wei Zhou ◽

Hongwei Zhang ◽

Yan Hu ◽

Lei Yu ◽

...

Keyword(s):

Breast Cancer ◽

Progesterone Receptor ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cancer Growth ◽

Membrane Progesterone Receptor ◽

Breast Cancer Growth ◽

The Brain

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Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20123080 ◽

2019 ◽

Vol 20 (12) ◽

pp. 3080 ◽

Cited By ~ 4

Author(s):

Fan Wu ◽

Robert D. McCuaig ◽

Christopher R. Sutton ◽

Abel H. Y. Tan ◽

Yoshni Jeelall ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastasis ◽

Cancer Progression ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Lung Metastases ◽

Her2 Positive ◽

Pathway Gene ◽

Dual Specificity ◽

The Brain

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.

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