Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research
Published in: Breast Cancer Research 3/2014

Open Access 01-06-2014 | Viewpoint

Breast cancer brain metastases: evidence for neuronal-like adaptation in a ‘breast-to-brain’ transition?

Authors: Amanda ED Van Swearingen, Marni B Siegel, Carey K Anders

Published in: Breast Cancer Research | Issue 3/2014

Login to get access

Abstract

Brain metastases remain a significant challenge in the treatment of breast cancer patients due to the unique environment posed by the central nervous system. A better understanding of the biology of breast cancer cells that have metastasized to the brain is required to develop improved therapies. A recent Proceedings of the National Academy of Sciences article demonstrates that breast cancer cells in the brain microenvironment express γ-aminobutyric acid (GABA)-related genes, enabling them to utilize GABA as an oncometabolite, thus gaining a proliferative advantage. In this viewpoint, we highlight these findings and their potential impact on the treatment of breast cancer brain metastases.
Literature
1.
Niwinska A, Murawska M, Pogoda K: Breast cancer brain metastases: differences in survival depending on biological subtype, RPA RTOG prognostic class and systemic treatment after whole-brain radiotherapy (WBRT). Ann Oncol. 2010, 21: 942-948. 10.1093/annonc/mdp407.CrossRefPubMed
2.
Ewend MG, Morris DE, Carey LA, Ladha AM, Brem S: Guidelines for the initial management of metastatic brain tumors: role of surgery, radiosurgery, and radiation therapy. J Natl Compr Canc Netw. 2008, 6: 505-513. quiz 514PubMed
3.
Harrell JC, Prat A, Parker JS, Fan C, He X, Carey L, Anders C, Ewend M, Perou CM: Genomic analysis identifies unique signatures predictive of brain, lung, and liver relapse. Breast Cancer Res Treat. 2012, 132: 523-535. 10.1007/s10549-011-1619-7.CrossRefPubMed
4.
Smid M, Wang Y, Zhang Y, Sieuwerts AM, Yu J, Klijn JG, Foekens JA, Martens JW: Subtypes of breast cancer show preferential site of relapse. Cancer Res. 2008, 68: 3108-3114. 10.1158/0008-5472.CAN-07-5644.CrossRefPubMed
5.
Valiente M, Obenauf AC, Jin X, Chen Q, Zhang XH, Lee DJ, Chaft JE, Kris MG, Huse JT, Brogi E, Massagué J: Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell. 2014, 156: 1002-1016. 10.1016/j.cell.2014.01.040.CrossRefPubMedPubMedCentral
6.
Wang L, Cossette SM, Rarick KR, Gershan J, Dwinell MB, Harder DR, Ramchandran R: Astrocytes directly influence tumor cell invasion and metastasis in vivo. PLoS One. 2013, 8: e80933-10.1371/journal.pone.0080933.CrossRefPubMedPubMedCentral
7.
Romagnoli M, Mineva ND, Polmear M, Conrad C, Srinivasan S, Loussouarn D, Barillé-Nion S, Georgakoudi I, Dagg A, McDermott EW, Duffy MJ, McGowan PM, Schlomann U, Parsons M, Bartsch JW, Sonenshein GE: ADAM8 expression in invasive breast cancer promotes tumor dissemination and metastasis. EMBO Mol Med. 2014, 6: 278-294.PubMed
8.
Malin D, Strekalova E, Petrovic V, Deal AM, Al Ahmad A, Adamo B, Miller CR, Ugolkov A, Livasy C, Fritchie K, Hamilton E, Blackwell K, Geradts J, Ewend M, Carey L, Shusta EV, Anders CK, Cryns VL: AlphaB-Crystallin: a novel regulator of breast cancer metastasis to the brain. Clin Cancer Res. 2014, 20: 56-67. 10.1158/1078-0432.CCR-13-1255.CrossRefPubMed
9.
Kim SJ, Kim JS, Park ES, Lee JS, Lin Q, Langley RR, Maya M, He J, Kim SW, Weihua Z, Balasubramanian K, Fan D, Mills GB, Hung MC, Fidler IJ: Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy. Neoplasia. 2011, 13: 286-298.CrossRefPubMedPubMedCentral
10.
Xing F, Kobayashi A, Okuda H, Watabe M, Pai SK, Pandey PR, Hirota S, Wilber A, Mo YY, Moore BE, Liu W, Fukuda K, Iiizumi M, Sharma S, Liu Y, Wu K, Peralta E, Watabe K: Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain. EMBO Mol Med. 2013, 5: 384-396. 10.1002/emmm.201201623.CrossRefPubMedPubMedCentral
11.
Neman J, Choy C, Kowolik CM, Anderson A, Duenas VJ, Waliany S, Chen BT, Chen MY, Jandial R: Co-evolution of breast-to-brain metastasis and neural progenitor cells. Clin Exp Metastasis. 2013, 30: 753-768. 10.1007/s10585-013-9576-7.CrossRefPubMed
12.
Fitzgerald DP, Palmieri D, Hua E, Hargrave E, Herring JM, Qian Y, Vega-Valle E, Weil RJ, Stark AM, Vortmeyer AO, Steeg PS: Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization. Clin Exp Metastasis. 2008, 25: 799-810. 10.1007/s10585-008-9193-z.CrossRefPubMedPubMedCentral
13.
Gril B, Palmieri D, Qian Y, Anwar T, Liewehr DJ, Steinberg SM, Andreu Z, Masana D, Fernández P, Steeg PS, Vidal-Vanaclocha F: Pazopanib inhibits the activation of PDGFRbeta-expressing astrocytes in the brain metastatic microenvironment of breast cancer cells. Am J Pathol. 2013, 182: 2368-2379. 10.1016/j.ajpath.2013.02.043.CrossRefPubMedPubMedCentral
14.
Gril B, Palmieri D, Qian Y, Smart D, Ileva L, Liewehr DJ, Steinberg SM, Steeg PS: Pazopanib reveals a role for tumor cell B-Raf in the prevention of HER2+ breast cancer brain metastasis. Clin Cancer Res. 2011, 17: 142-153. 10.1158/1078-0432.CCR-10-1603.CrossRefPubMed
15.
Neman J, Termini J, Wilczynski S, Vaidehi N, Choy C, Kowolik CM, Li H, Hambrecht AC, Roberts E, Jandial R: Human breast cancer metastases to the brain display GABAergic properties in the neural niche. Proc Natl Acad Sci U S A. 2014, 111: 984-989. 10.1073/pnas.1322098111.CrossRefPubMedPubMedCentral
16.
Park ES, Kim SJ, Kim SW, Yoon SL, Leem SH, Kim SB, Kim SM, Park YY, Cheong JH, Woo HG, Mills GB, Fidler IJ, Lee JS: Cross-species hybridization of microarrays for studying tumor transcriptome of brain metastasis. Proc Natl Acad Sci U S A. 2011, 108: 17456-17461. 10.1073/pnas.1114210108.CrossRefPubMedPubMedCentral
17.
Paget S: The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 1989, 8: 98-101.PubMed
18.
Fidler IJ: The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003, 3: 453-458. 10.1038/nrc1098.CrossRefPubMed
19.
Warburg O: On the origin of cancer cells. Science. 1956, 123: 309-314. 10.1126/science.123.3191.309.CrossRefPubMed
20.
Madsen KK, Larsson OM, Schousboe A: Regulation of excitation by GABA neurotransmission: focus on metabolism and transport. Results Probl Cell Differ. 2008, 44: 201-221. 10.1007/400_2007_036.CrossRefPubMed
Metadata
Title
Breast cancer brain metastases: evidence for neuronal-like adaptation in a ‘breast-to-brain’ transition?
Authors
Amanda ED Van Swearingen
Marni B Siegel
Carey K Anders
Publication date
01-06-2014
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2014
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3651

Other articles of this Issue 3/2014

Breast Cancer Research 3/2014 Go to the issue

Research article

Survivin family proteins as novel molecular determinants of doxorubicin resistance in organotypic human breast tumors

Research article

Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity

Review

Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers

Review

Breast-related effects of selective estrogen receptor modulators and tissue-selective estrogen complexes

Research article

C-X-C motif chemokine 12/C-X-C chemokine receptor type 7 signaling regulates breast cancer growth and metastasis by modulating the tumor microenvironment

Editorial

Endocrine therapy: defining the path of least resistance
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits