Online citations, reference lists, and bibliographies.
← Back to Search

Breast Cancer Brain Metastases

X. Cheng, M. Hung
Published 2007 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Breast cancer is the most common malignancy in woman in the USA. Metastasis is a major cause of morbidity and mortality in breast cancer patients. Total incidence of brain metastases of breast cancer is about 30%. Because of the improvements in control of systemic disease, for example the successful use of Trastuzumab, and the consequent prolonged life span, the incidence of brain metastases is increasing in breast cancer patients. The progressive neurological disabilities not only impair the quality of life, but also decrease the survival in patients. However, current treatments are of limited effectiveness. This is partially caused by the unique structure of the blood brain barrier. So far very little is known about the mechanisms how breast cancer metastizes to the brain. Some studies showed that ErbB2 overexpression is associated with the brain metastatic phenotype. Other molecules, like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs) and chemokine receptor CXCR4 are also involved in the metastasis of breast cancer cell to the brain. The current review will briefly overview the clinical features of brain metastasis of breast cancer and discusses the relationship of blood brain barrier and ErbB2 signal pathway to brain metastasis in breast cancer.
This paper references
Diagnostic Evaluation of Neurologic Metastases
S. Jeyapalan (2000)
Brain Metastases — Comparison of Gadodiamide Injection-Enhanced MR Imaging at Standard and High Dose, Contrast-Enhanced CT and Non-Contrast-Enhanced MR Imaging
P. Åkeson (1995)
Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis.
Y. Li (2004)
Prognostic factors in patients with brain metastases.
F. Lagerwaard (2001)
Diagnostic Accuracy of MRI Compared to CCT in Patients with Brain Metastases
P. Schellinger (2004)
HER2 in brain metastases: issues of concordance, survival, and treatment.
I. Fuchs (2002)
Leptomeningeal metastases.
S. Kesari (2003)
Diagnosis of cerebral metastases: double-dose delayed CT vs contrast-enhanced MR imaging.
P. Davis (1991)
neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.
I. Andrulis (1998)
Role of host microenvironment in angiogenesis and microvascular functions in human breast cancer xenografts: mammary fat pad versus cranial tumors.
W. Monsky (2002)
CNS metastases in breast cancer.
N. Lin (2004)
Meningeal carcinomatosis in patients with breast carcinoma: Clinical features, prognostic factors, and results of a high‐dose intrathecal methotrexate regimen
K. Fizazi (1996)
Differential Expression of Matrix Metalloproteinases in Brain- and Bone-Seeking Clones of Metastatic MDA-MB-231 Breast Cancer Cells
A. Stark (2006)
Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases.
J. Suh (2006)
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D. Slamon (1987)
Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer.
Z. Gabos (2006)
Breast Cancer: Metastatic Patterns and Their Prognosis
O. Salazar (1988)
Prognostic factors in early breast carcinoma
Edward G. Mansour (1994)
Primary breast
Y. L. Tham (2006)
Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer.
F. André (2006)
Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials.
L. Gaspar (1997)
Trastuzumab for breast cancer-related carcinomatous meningitis.
H. Robins (2002)
Correlation of vascular endothelial growth factor content with recurrences, survival, and first relapse site in primary node-positive breast carcinoma after adjuvant treatment.
B. Linderholm (2000)
Increased ICAM-1 expression causes endothelial cell leakiness, cytoskeletal reorganization and junctional alterations.
P. R. Clark (2007)
Advances in Targeting Human Epidermal Growth Factor Receptor-2 Signaling for Cancer Therapy
F. Meric-Bernstam (2006)
Brain metastases.
R. Patchell (1991)
Breast cancer metastasis to the central nervous system.
R. Weil (2005)
Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System.
J. Barnholtz-Sloan (2004)
The organ microenvironment and cancer metastasis.
I. Fidler (2002)
Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment.
E. Shmueli (2004)
The biology of erbB-2/neu/HER-2 and its role in cancer.
N. E. Hynes (1994)
Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG).
B. Pestalozzi (2006)
Characteristics of patients with brain metastases receiving trastuzumab for HER2 overexpressing metastatic breast cancer.
H. Stemmler (2006)
Phosphorylation/Cytoplasmic Localization of p21Cip1/WAF1 Is Associated with HER2/neu Overexpression and Provides a Novel Combination Predictor for Poor Prognosis in Breast Cancer Patients
W. Xia (2004)
Determinants and prognoses of locoregional and distant progression in breast cancer.
J. Engel (2003)
Prognostic factors in patients with brain metastases.
Lagerwaard Fj (2001)
The diagnostic accuracy of magnetic resonance imaging and cerebrospinal fluid cytology in leptomeningeal metastasis
C. Straathof (1999)
Central nervous system metastasis from breast carcinoma autopsy study
Y. Tsukada (1983)
Breast carcinoma: Pattern of metastasis at autopsy
Y. Lee (1983)
Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status
J. Souglakos (2006)
Pro-Matrix Metalloproteinase-2 Transfection Increases Orthotopic Primary Growth and Experimental Metastasis of MDA-MB-231 Human Breast Cancer Cells in Nude Mice
Angus M. Tester (2004)
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
D. Slamon (1989)
Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer
A. Clayton (2004)
Causes of death and metastatic patterns in patients with mammary cancer. Ten-year autopsy study.
S. Y. Cho (1980)
Multiple brain metastases are associated with poor survival in patients treated with surgery and radiotherapy.
M. Hazuka (1993)
Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells
B. Zhou (2001)
Efficacy of intracerebral microinfusion of trastuzumab in an athymic rat model of intracerebral metastatic breast cancer.
Peter M. Grossi (2003)
Lapatinib: a dual inhibitor of EGFR and HER2 tyrosine kinase activity
F. Montemurro (2007)
Erk Associates with and Primes GSK-3β for Its Inactivation Resulting in Upregulation of β-Catenin
Q. Ding (2005)
Interstitial chemotherapy with carmus - tine - loaded polymers for high - grade gliomas : A randomized double - blind study
P. M. Grossi (2003)
Increased risk of brain metastases in patients with HER‐2/neu‐positive breast carcinoma
R. Altaha (2005)
Central nervous system metastases in women who receive trastuzumab‐based therapy for metastatic breast carcinoma
J. Bendell (2003)
The ErbB signaling network: receptor heterodimerization in development and cancer
M. Olayioye (2000)
Association of C‐erbB‐2 protein over‐expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long‐term survival in breast cancer
O. Kallioniemi (1991)
Breast Cancers With Brain Metastases are More Likely to be Estrogen Receptor Negative, Express the Basal Cytokeratin CK5/6, and Overexpress HER2 or EGFR
D. Hicks (2006)
HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation
B. Zhou (2001)
A randomized trial of surgery in the treatment of single metastases to the brain.
R. Patchell (1990)
Vascular endothelial growth factor expression promotes the growth of breast cancer brain metastases in nude mice
L. Kim (2004)
neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer
P. Ravdin (1999)
Surgical treatment of multiple brain metastases.
R. Bindal (1993)
Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival.
K. Miller (2003)
Erk associates with and primes GSK-3beta for its inactivation resulting in upregulation of beta-catenin.
Q. Ding (2005)
Expression of MMP2, MMP9 and MMP3 in Breast Cancer Brain Metastasis in a Rat Model
O. Mendes (2005)
Current therapeutic approaches in patients with brain metastases
Kevin H Peacock (2006)
Overexpression of ErbB 2 in cancer and ErbB 2 - targeting strategies
M. C. Hung (2000)
Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood–brain barrier
H. Stemmler (2007)
Overexpression of ErbB2 in cancer and ErbB2-targeting strategies
D. Yu (2000)
Her-2/neu as a Predictive Marker of Response to Breast Cancer Therapy
M. Pegram (2004)
Treatment of meningeal breast cancer xenografts in the rat using an anti-p185/HER2 antibody.
I. Bergman (2001)
The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells
B. C. Schmid (2007)
Early phase I data on an irreversible pan-erb inhibitor: CI-1033
M. R. Dewji (2004)
What did We Learn
A. Zohar (2004)
Oncogenic Signals of HER-2/neu in Regulating the Stability of the Cyclin-dependent Kinase Inhibitor p27*
H. A. Yang (2000)
Detection of brain metastases: comparison of contrast-enhanced MR with unenhanced MR and enhanced CT.
G. Sze (1990)
Involvement of chemokine receptors in breast cancer metastasis
A. Müller (2001)
Headaches in patients with brain tumors
P. Forsyth (1993)
Early Phase I Data on an Irreversible Pan-Er Inhibitor: CI-1033. What Did We Learn?
M. Dewji (2004)
Incidence, pattern and timing of brain metastases among patients with advanced breast cancer treated with trastuzumab
T. Yau (2006)
Vascular Endothelial Growth Factor Modulates the Transendothelial Migration of MDA-MB-231 Breast Cancer Cells through Regulation of Brain Microvascular Endothelial Cell Permeability*
Tae-Hee Lee (2003)
Survival of patients with metastatic breast carcinoma
J. Chang (2003)
Primary breast cancer phenotypes associated with propensity for central nervous system metastases
Y. Tham (2006)
Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.
D. Slamon (2001)
Identification of a specific DNA region required for enhanced transcription of HER2/neu in the MDA-MB453 breast cancer cell line.
S. Miller (1996)
The blood–brain barrier: an overview: Structure, regulation, and clinical implications
P. Ballabh (2004)
ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/p70S6K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells.
K. Klos (2006)
Traversal of Candida albicans across Human Blood-Brain Barrier In Vitro
A. Jong (2001)
The organ microenvironment and cancer
I. J. Fidler (2002)
Interstitial chemotherapy with carmustine-loaded polymers for high-grade gliomas: a randomized double-blind study.
S. Valtonen (1997)
Involvement of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1alpha in breast cancer cell migration through human brain microvascular endothelial cells.
Byeong-Chel Lee (2004)

This paper is referenced by
Chapter 9 – New Targeted Therapies for Brain Metastases from Breast and Lung Cancer and Melanoma
Emmanouil Fokas (2015)
Systemic high-dose intravenous methotrexate in patients with central nervous system metastatic breast cancer
Fernando Fernández Bazán (2019)
Preclinical Evaluation of Oncolytic Δγ 134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases
J. J. Cody (2012)
Evaluation of Radiation Dose-Response in a Breast Cancer Brain Metastasis Model
Niloufar Zarghami (2015)
Current state of clinical trials in breast cancer brain metastases.
Jawad Fares (2019)
Breast Cancer and Renal Cell Cancer Metastases to the Brain
Jonas M. Sheehan (2011)
Monoclonal antibodies in neuro-oncology
L. Lampson (2011)
Clinical analysis of patients with central nervous system metastases from breast cancer
L. Gottwald (2012)
Cooperation of neurotrophin receptor TrkB and Her2 in breast cancer cells facilitates brain metastases
Cecilia Choy (2017)
The Role of Type I Insulin-Like Growth Factor Receptor Signaling in Breast Cancer Brain Metastasis
Sandra M. Saldana (2013)
The Role of Astrocytes in Tumor Growth and Progression
Emily I Gronseth (2018)
Establishment of an ovarian metastasis model and possible involvement of E‐cadherin down‐regulation in the metastasis
Y. Kuwabara (2008)
OSM-induced CD44 contributes to breast cancer metastatic potential through cell detachment but not epithelial-mesenchymal transition
Hunter Covert (2019)
Pharmaceutical Perspectives of Cancer Therapeutics: Current Therapeutic Uses of Monoclonal Antibodies
M. D. Axelson (2009)
Pharmacokinetics and efficacy of pemetrexed in patients with brain or leptomeningeal metastases
P. Kumthekar (2013)
External validation of a published nomogram for prediction of brain metastasis in patients with extra-cerebral metastatic breast cancer and risk regression analysis.
Ludivine Genre (2017)
Predictive factors of brain metastasis in patients with breast cancer
Jun Xue (2013)
Brain Metastases Progression of Breast Cancer
A. A. Moustafa (2011)
Human brain endothelial cell-derived COX-2 facilitates extravasation of breast cancer cells across the blood-brain barrier.
K. Y. Lee (2011)
Is active targeting of brain metastases of breast cancer superior to passive targeting
N. Kamal (2019)
The role of Pim-1 in breast cancer metastasis
Lara Jupp (2017)
Ulcerated breast cancer with single brain metastasis: A combined surgical approach. Clinical presentation at one year follow up – A case report
Francesca Santori (2020)
Emerging role of brain metastases in the prognosis of breast cancer patients.
Amanda Hambrecht (2011)
Brain Metastasis of Breast Cancer: Crossing the Blood-brain Barrier
J. Li (2017)
Interaction of tumor cells and astrocytes promotes breast cancer brain metastases through TGF-β2/ANGPTL4 axes
X. Gong (2019)
Roles of the Cyclooxygenase 2 Matrix Metalloproteinase 1 Pathway in Brain Metastasis of Breast Cancer*
K. Wu (2015)
Inhibition of Type I Insulin-Like Growth Factor Receptor Signaling Attenuates the Development of Breast Cancer Brain Metastasis
Sandra M. Saldana (2013)
Identification and Analysis of Signaling Networks Potentially Involved in Breast Carcinoma Metastasis to the Brain
Feng Li (2011)
Advanced Screening and Integrative Analysis for Biotechnology and Disease
M. Burnette (2016)
Origins of metastatic traits.
S. Vanharanta (2013)
Emerging treatment options for the management of brain metastases in patients with HER2-positive metastatic breast cancer
A. Chien (2012)
Apparent diffusion coefficient histogram in breast cancer brain metastases may predict their biological subtype and progression
S. J. Ahn (2018)
See more
Semantic Scholar Logo Some data provided by SemanticScholar