. 2016 Jan; 18(1):8.
doi: 10.1186/s13058-015-0665-1.

Breast cancer brain metastases: biology and new clinical perspectives

Isabell Witzel 1 Leticia Oliveira-Ferrer 2 Klaus Pantel 3 Volkmar Müller 4 Harriet Wikman 5 
  • PMID: 26781299
  •     87 References
  •     70 citations


Because of improvements in the treatment of patients with metastatic breast cancer, the development of brain metastases (BM) has become a major limitation of life expectancy and quality of life for many breast cancer patients. The improvement of management strategies for BM is thus an important clinical challenge, especially among high-risk patients such as human epidermal growth factor receptor 2-positive and triple-negative patients. However, the formation of BM as a multistep process is thus far poorly understood. To grow in the brain, single tumor cells must pass through the tight blood-brain barrier (BBB). The BBB represents an obstacle for circulating tumor cells entering the brain, but it also plays a protective role against immune cell and toxic agents once metastatic cells have colonized the cerebral compartment. Furthermore, animal studies have shown that, after passing the BBB, the tumor cells not only require close contact with endothelial cells but also interact closely with many different brain residential cells. Thus, in addition to a genetic predisposition of the tumor cells, cellular adaptation processes within the new microenvironment may also determine the ability of a tumor cell to metastasize. In this review, we summarize the biology of breast cancer that has spread into the brain and discuss the implications for current and potential future treatment strategies.

Management of patients with brain metastases receiving trastuzumab treatment for metastatic breast cancer.
Isabell Witzel, Eva Johanna Kantelhardt, +5 authors, Volkmar Müller.
Onkologie, 2011 Jun 01; 34(6). PMID: 21625183
Characterization of metastatic breast cancer patients with nondetectable circulating tumor cells.
Michal Mego, Ugo De Giorgi, +7 authors, Massimo Cristofanilli.
Int J Cancer, 2010 Sep 22; 129(2). PMID: 20857493
Preclinical recapitulation of antiangiogenic drug clinical efficacies using models of early or late stage breast cancer metastatis.
Robert S Kerbel, Eric Guerin, +4 authors, Shan Man.
Breast, 2013 Oct 01; 22 Suppl 2. PMID: 24074794
Detection of circulating tumor DNA in early- and late-stage human malignancies.
Chetan Bettegowda, Mark Sausen, +60 authors, Luis A Diaz.
Sci Transl Med, 2014 Feb 21; 6(224). PMID: 24553385    Free PMC article.
Highly Cited.
REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours.
C Lévy, D Allouache, +21 authors, X Paoletti.
Ann Oncol, 2014 Oct 03; 25(12). PMID: 25274615
The identification and characterization of breast cancer CTCs competent for brain metastasis.
Lixin Zhang, Lon D Ridgway, +6 authors, Dario Marchetti.
Sci Transl Med, 2013 Apr 12; 5(180). PMID: 23576814    Free PMC article.
Highly Cited.
Challenges in circulating tumour cell research.
Catherine Alix-Panabières, Klaus Pantel.
Nat Rev Cancer, 2014 Aug 27; 14(9). PMID: 25154812
Highly Cited. Review.
Angiopoietin-2 mediates blood-brain barrier impairment and colonization of triple-negative breast cancer cells in brain.
Hava Karsenty Avraham, Shuxian Jiang, +3 authors, Shalom Avraham.
J Pathol, 2014 Jan 15; 232(3). PMID: 24421076
Review: activation patterns of microglia and their identification in the human brain.
D Boche, V H Perry, J A R Nicoll.
Neuropathol Appl Neurobiol, 2012 Dec 21; 39(1). PMID: 23252647
Highly Cited. Review.
Hepatocyte growth factor enhances adhesion of breast cancer cells to endothelial cells in vitro through up-regulation of CD44.
Shinichiro Mine, Takeshi Fujisaki, +5 authors, Yoshiya Tanaka.
Exp Cell Res, 2003 Jul 25; 288(1). PMID: 12878170
Astrocytes directly influence tumor cell invasion and metastasis in vivo.
Ling Wang, Stephanie M Cossette, +4 authors, Ramani Ramchandran.
PLoS One, 2013 Dec 11; 8(12). PMID: 24324647    Free PMC article.
Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab.
E M Olson, M Abdel-Rasoul, +3 authors, C L Shapiro.
Ann Oncol, 2013 Mar 07; 24(6). PMID: 23463626    Free PMC article.
Incidence and patterns of distant metastases for patients with early-stage breast cancer after breast conservation treatment.
Abigail T Berman, Arpi D Thukral, +2 authors, Neha Vapiwala.
Clin Breast Cancer, 2012 Dec 12; 13(2). PMID: 23218473
Incidence, pattern and timing of brain metastases among patients with advanced breast cancer treated with trastuzumab.
Thomas Yau, Charles Swanton, +6 authors, Ian E Smith.
Acta Oncol, 2006 Mar 21; 45(2). PMID: 16546866
Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition.
Ingrid Espinoza, Radhika Pochampally, +2 authors, Lucio Miele.
Onco Targets Ther, 2013 Sep 18; 6. PMID: 24043949    Free PMC article.
Highly Cited. Review.
Mammary carcinoma cell lines of high and low metastatic potential differ not in extravasation but in subsequent migration and growth.
V L Morris, S Koop, +5 authors, A C Groom.
Clin Exp Metastasis, 1994 Nov 01; 12(6). PMID: 7923988
Genes that mediate breast cancer metastasis to the brain.
Paula D Bos, Xiang H-F Zhang, +8 authors, Joan Massagué.
Nature, 2009 May 08; 459(7249). PMID: 19421193    Free PMC article.
Highly Cited.
Treatment outcomes and prognostic factors for patients with brain metastases from breast cancer of each subtype: a multicenter retrospective analysis.
Naoki Niikura, Naoki Hayashi, +17 authors, Hiroji Iwata.
Breast Cancer Res Treat, 2014 Aug 12; 147(1). PMID: 25106661
Serpins promote cancer cell survival and vascular co-option in brain metastasis.
Manuel Valiente, Anna C Obenauf, +8 authors, Joan Massagué.
Cell, 2014 Mar 04; 156(5). PMID: 24581498    Free PMC article.
Highly Cited.
Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases.
Barbara Adamo, Allison M Deal, +11 authors, Carey K Anders.
Breast Cancer Res, 2011 Dec 03; 13(6). PMID: 22132754    Free PMC article.
The vascular basement membrane as "soil" in brain metastasis.
W Shawn Carbonell, Olaf Ansorge, Nicola Sibson, Ruth Muschel.
PLoS One, 2009 Jun 12; 4(6). PMID: 19516901    Free PMC article.
Highly Cited.
Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy.
Sun-Jin Kim, Jang-Seong Kim, +12 authors, Isaiah J Fidler.
Neoplasia, 2011 Mar 11; 13(3). PMID: 21390191    Free PMC article.
Highly Cited.
Subtypes of breast cancer show preferential site of relapse.
Marcel Smid, Yixin Wang, +5 authors, John W M Martens.
Cancer Res, 2008 May 03; 68(9). PMID: 18451135
Highly Cited.
Carcinoma cells misuse the host tissue damage response to invade the brain.
Han-Ning Chuang, Denise van Rossum, +12 authors, Tobias Pukrop.
Glia, 2013 Jul 09; 61(8). PMID: 23832647    Free PMC article.
Lapatinib distribution in HER2 overexpressing experimental brain metastases of breast cancer.
Kunal S Taskar, Vinay Rudraraju, +12 authors, Quentin R Smith.
Pharm Res, 2011 Oct 21; 29(3). PMID: 22011930    Free PMC article.
Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neu-positive breast cancer.
Kan Yonemori, Koji Tsuta, +7 authors, Yasuhiro Fujiwara.
Cancer, 2009 Nov 26; 116(2). PMID: 19937674
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, Hava Karsenty Avraham, Shuxian Jiang, Shalom Avraham.
J Biol Chem, 2002 Nov 26; 278(7). PMID: 12446667
Breast cancer brain metastases responding to primary systemic therapy with T-DM1.
Rupert Bartsch, Anna S Berghoff, Matthias Preusser.
J Neurooncol, 2013 Sep 26; 116(1). PMID: 24065570
Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain.
Diane Palmieri, Julie L Bronder, +11 authors, Patricia S Steeg.
Cancer Res, 2007 May 08; 67(9). PMID: 17483330
Highly Cited.
Recent trends in epidemiology of brain metastases: an overview.
Emeline Tabouret, Olivier Chinot, +3 authors, Anthony Gonçalves.
Anticancer Res, 2012 Nov 17; 32(11). PMID: 23155227
Activation of notch signaling in a xenograft model of brain metastasis.
Do-Hyun Nam, Hye-Min Jeon, +9 authors, Woong-Yang Park.
Clin Cancer Res, 2008 Jul 03; 14(13). PMID: 18593982
Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer.
Jochen Gaedcke, Frank Traub, +6 authors, Hans H Kreipe.
Mod Pathol, 2007 Jun 02; 20(8). PMID: 17541441
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, Tae-Hee Lee, Shalom Avraham, Hava Karsenty Avraham.
Mol Cancer Res, 2004 Jul 06; 2(6). PMID: 15235108
Vascular endothelial growth factor expression promotes the growth of breast cancer brain metastases in nude mice.
Lee Su Kim, Suyung Huang, +2 authors, Janet E Price.
Clin Exp Metastasis, 2004 Jun 01; 21(2). PMID: 15168728
The shifting landscape of metastatic breast cancer to the CNS.
Matthew R Quigley, Olivia Fukui, +2 authors, Steven Karlovits.
Neurosurg Rev, 2012 Dec 25; 36(3). PMID: 23262837
The distribution of secondary growths in cancer of the breast. 1889.
S Paget.
Cancer Metastasis Rev, 1989 Aug 01; 8(2). PMID: 2673568
Highly Cited.
Involvement of epidermal growth factor receptor overexpression in the promotion of breast cancer brain metastasis.
Fang Nie, Jian Yang, +9 authors, Gao-Jun Teng.
Cancer, 2012 Apr 19; 118(21). PMID: 22510844
Breast cancer: metastatic patterns and their prognosis.
V Patanaphan, O M Salazar, R Risco.
South Med J, 1988 Sep 01; 81(9). PMID: 3420442
Systemic treatments for brain metastases from breast cancer, non-small cell lung cancer, melanoma and renal cell carcinoma: an overview of the literature.
Giuseppe Lombardi, Anna Luisa Di Stefano, +2 authors, Emeline Tabouret.
Cancer Treat Rev, 2014 Jun 10; 40(8). PMID: 24909312
Glioblastoma: molecular pathways, stem cells and therapeutic targets.
Meena Jhanwar-Uniyal, Michael Labagnara, +2 authors, Raj Murali.
Cancers (Basel), 2015 Mar 31; 7(2). PMID: 25815458    Free PMC article.
Clinical relevance of loss of 11p15 in primary and metastatic breast cancer: association with loss of PRKCDBP expression in brain metastases.
Harriet Wikman, Bettina Sielaff-Frimpong, +6 authors, Klaus Pantel.
PLoS One, 2012 Nov 03; 7(10). PMID: 23118876    Free PMC article.
The dandelion effect: treat the whole lawn or weed selectively?
Minesh Mehta.
J Clin Oncol, 2010 Dec 08; 29(2). PMID: 21135269
Transmigration of melanoma cells through the blood-brain barrier: role of endothelial tight junctions and melanoma-released serine proteases.
Csilla Fazakas, Imola Wilhelm, +9 authors, István A Krizbai.
PLoS One, 2011 Jun 16; 6(6). PMID: 21674054    Free PMC article.
Selection of brain metastasis-initiating breast cancer cells determined by growth on hard agar.
Lixia Guo, Dominic Fan, +5 authors, Robert R Langley.
Am J Pathol, 2011 Apr 26; 178(5). PMID: 21514446    Free PMC article.
Breast cancer subtypes and response to systemic treatment after whole-brain radiotherapy in patients with brain metastases.
Anna Niwińska, Magdalena Murawska, Katarzyna Pogoda.
Cancer, 2010 Jun 16; 116(18). PMID: 20549816
Biological subtypes and survival outcomes in breast cancer patients with brain metastases (study of the Anatolian Society of Medical Oncology).
Muhammet Ali Kaplan, Abdurrahman Isikdogan, +22 authors, Suleyman Buyukberber.
Oncology, 2012 Jul 21; 83(3). PMID: 22814315
Bevacizumab preconditioning followed by Etoposide and Cisplatin is highly effective in treating brain metastases of breast cancer progressing from whole-brain radiotherapy.
Yen-Shen Lu, Tom Wei-Wu Chen, +11 authors, Taiwan Breast Cancer Consortium.
Clin Cancer Res, 2015 Feb 24; 21(8). PMID: 25700303
Metastatic behavior of breast cancer subtypes.
Hagen Kennecke, Rinat Yerushalmi, +5 authors, Karen Gelmon.
J Clin Oncol, 2010 May 26; 28(20). PMID: 20498394
Highly Cited.
Frequent genetic alterations in EGFR- and HER2-driven pathways in breast cancer brain metastases.
Ina Hohensee, Katrin Lamszus, +9 authors, Harriet Wikman.
Am J Pathol, 2013 May 15; 183(1). PMID: 23665199
Real-time imaging reveals the single steps of brain metastasis formation.
Yvonne Kienast, Louisa von Baumgarten, +4 authors, Frank Winkler.
Nat Med, 2009 Dec 22; 16(1). PMID: 20023634
Highly Cited.
Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain.
Fei Xing, Aya Kobayashi, +15 authors, Kounosuke Watabe.
EMBO Mol Med, 2013 Mar 16; 5(3). PMID: 23495140    Free PMC article.
Breast carcinoma: pattern of metastasis at autopsy.
Y T Lee.
J Surg Oncol, 1983 Jul 01; 23(3). PMID: 6345937
Highly Cited. Review.
Microglia promote colonization of brain tissue by breast cancer cells in a Wnt-dependent way.
Tobias Pukrop, Faramarz Dehghani, +14 authors, Claudia Binder.
Glia, 2010 Jun 16; 58(12). PMID: 20549749
Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: a prospective study.
Aki Morikawa, David M Peereboom, +10 authors, Andrew D Seidman.
Neuro Oncol, 2014 Jul 13; 17(2). PMID: 25015089    Free PMC article.
Highly Cited.
Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study.
Harri Sihto, Johan Lundin, +9 authors, Heikki Joensuu.
Breast Cancer Res, 2011 Sep 15; 13(5). PMID: 21914172    Free PMC article.
Adjuvant whole-brain radiation therapy after surgical resection of single brain metastases.
Christopher M McPherson, Dima Suki, +4 authors, Frederick F Lang.
Neuro Oncol, 2010 Feb 17; 12(7). PMID: 20156806    Free PMC article.
Increased permeability of the blood-brain barrier to chemotherapy in metastatic brain tumors: establishing a treatment paradigm.
Elizabeth R Gerstner, Robert L Fine.
J Clin Oncol, 2007 Jun 01; 25(16). PMID: 17538177
CEREBEL (EGF111438): A Phase III, Randomized, Open-Label Study of Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.
Xavier Pivot, Alexey Manikhas, +18 authors, Vladimir Semiglazov.
J Clin Oncol, 2015 Jan 22; 33(14). PMID: 25605838
Highly Cited.
Co-overexpression of HER2/HER3 is a predictor of impaired survival in breast cancer patients.
Anna S Berghoff, Rupert Bartsch, +10 authors, Peter Birner.
Breast, 2014 Jul 16; 23(5). PMID: 25017122
Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma.
Leo J Schouten, Joost Rutten, Hans A M Huveneers, Albert Twijnstra.
Cancer, 2002 Aug 14; 94(10). PMID: 12173339
Highly Cited.
First-line bevacizumab-paclitaxel in 220 patients with metastatic breast cancer: results from the AVAREG study.
Magdolna Dank, Laszlo Budi, +5 authors, Laszlo Landherr.
Anticancer Res, 2014 Mar 07; 34(3). PMID: 24596372
Loss of CADM1 expression is associated with poor prognosis and brain metastasis in breast cancer patients.
Harriet Wikman, Laura Westphal, +16 authors, Klaus Pantel.
Oncotarget, 2014 May 17; 5(10). PMID: 24833255    Free PMC article.
Fine structural localization of a blood-brain barrier to exogenous peroxidase.
T S Reese, M J Karnovsky.
J Cell Biol, 1967 Jul 01; 34(1). PMID: 6033532    Free PMC article.
Highly Cited.
Capturing changes in the brain microenvironment during initial steps of breast cancer brain metastasis.
Mihaela Lorger, Brunhilde Felding-Habermann.
Am J Pathol, 2010 Apr 13; 176(6). PMID: 20382702    Free PMC article.
Highly Cited.
Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.
S Yano, H Shinohara, +6 authors, I J Fidler.
Cancer Res, 2000 Sep 15; 60(17). PMID: 10987313
Epidermal growth factor receptor status in breast cancer metastases to the central nervous system. Comparison with HER-2/neu status.
Nichon L Grupka, Kelly C Lear-Kaul, Bette K Kleinschmidt-DeMasters, Meenakshi Singh.
Arch Pathol Lab Med, 2004 Sep 01; 128(9). PMID: 15335267
Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA.
I E Krop, N U Lin, +7 authors, V Diéras.
Ann Oncol, 2014 Oct 31; 26(1). PMID: 25355722    Free PMC article.
Highly Cited.
Brain tumor cells in circulation are enriched for mesenchymal gene expression.
James P Sullivan, Brian V Nahed, +17 authors, Daniel A Haber.
Cancer Discov, 2014 Aug 21; 4(11). PMID: 25139148    Free PMC article.
Highly Cited.
Metastatic progression of breast cancer: insights from 50 years of autopsies.
Margaret C Cummings, Peter T Simpson, +9 authors, Sunil R Lakhani.
J Pathol, 2013 Oct 15; 232(1). PMID: 24122263    Free PMC article.
Hematogenous dissemination of glioblastoma multiforme.
Carolin Müller, Johannes Holtschmidt, +15 authors, Sabine Riethdorf.
Sci Transl Med, 2014 Aug 01; 6(247). PMID: 25080476
Highly Cited.
CNS metastases in breast cancer.
Nancy U Lin, Jennifer R Bellon, Eric P Winer.
J Clin Oncol, 2004 Sep 01; 22(17). PMID: 15337811
Highly Cited. Review.
Astrocyte-derived cytokines contribute to the metastatic brain specificity of breast cancer cells.
A Sierra, J E Price, +3 authors, A Fabra.
Lab Invest, 1997 Nov 14; 77(4). PMID: 9354770
Breast cancer subtypes predispose the site of distant metastases.
Abha Soni, Zhiyong Ren, +4 authors, Shi Wei.
Am J Clin Pathol, 2015 Mar 18; 143(4). PMID: 25779997
CD44 potentiates the adherence of metastatic prostate and breast cancer cells to bone marrow endothelial cells.
Jayne E Draffin, Suzanne McFarlane, +2 authors, David J J Waugh.
Cancer Res, 2004 Aug 18; 64(16). PMID: 15313910
HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer.
Leonard Da Silva, Peter T Simpson, +26 authors, Sunil R Lakhani.
Breast Cancer Res, 2010 Jul 08; 12(4). PMID: 20604919    Free PMC article.
Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): a single-group phase 2 study.
Thomas Bachelot, Gilles Romieu, +13 authors, Catherine Labbe-Devilliers.
Lancet Oncol, 2012 Nov 06; 14(1). PMID: 23122784
Highly Cited.
EGFR expression and gene copy number in triple-negative breast carcinoma.
Berrak Gumuskaya, Murat Alper, +3 authors, Gulnur Guler.
Cancer Genet Cytogenet, 2010 Dec 16; 203(2). PMID: 21156237
Notch1 inhibition alters the CD44hi/CD24lo population and reduces the formation of brain metastases from breast cancer.
Patricia M McGowan, Carmen Simedrea, +5 authors, Ann F Chambers.
Mol Cancer Res, 2011 Jun 15; 9(7). PMID: 21665937    Free PMC article.
Brain metastasis and response to ado-trastuzumab emtansine: a case report and literature review.
Richa Kalsi, Steven Feigenberg, +3 authors, Saranya Chumsri.
Clin Breast Cancer, 2014 Dec 03; 15(2). PMID: 25454740
Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer.
Paul R Lockman, Rajendar K Mittapalli, +11 authors, Quentin R Smith.
Clin Cancer Res, 2010 Sep 11; 16(23). PMID: 20829328    Free PMC article.
Highly Cited.
Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization.
Daniel P Fitzgerald, Diane Palmieri, +8 authors, Patricia S Steeg.
Clin Exp Metastasis, 2008 Jul 24; 25(7). PMID: 18649117    Free PMC article.
Metastasis results from preexisting variant cells within a malignant tumor.
I J Fidler, M L Kripke.
Science, 1977 Aug 26; 197(4306). PMID: 887927
Highly Cited.
Heregulin-HER3-HER2 signaling promotes matrix metalloproteinase-dependent blood-brain-barrier transendothelial migration of human breast cancer cell lines.
Majid Momeny, Jodi M Saunus, +11 authors, Sunil R Lakhani.
Oncotarget, 2015 Feb 11; 6(6). PMID: 25668816    Free PMC article.
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.
Hans-Joachim Stemmler, Manfred Schmitt, +3 authors, Volker Heinemann.
Anticancer Drugs, 2006 Dec 13; 18(1). PMID: 17159499
Human breast cancer metastases to the brain display GABAergic properties in the neural niche.
Josh Neman, John Termini, +7 authors, Rahul Jandial.
Proc Natl Acad Sci U S A, 2014 Jan 08; 111(3). PMID: 24395782    Free PMC article.
Highly Cited.
Notch-EGFR/HER2 Bidirectional Crosstalk in Breast Cancer.
Andrew T Baker, Andrei Zlobin, Clodia Osipo.
Front Oncol, 2015 Jan 08; 4. PMID: 25566499    Free PMC article.
Role of the neural niche in brain metastatic cancer.
John Termini, Josh Neman, Rahul Jandial.
Cancer Res, 2014 Jul 19; 74(15). PMID: 25035392    Free PMC article.
Metastatic breast cancer: The Odyssey of personalization.
A Sonnenblick, N Pondé, M Piccart.
Mol Oncol, 2016 Jul 20; 10(8). PMID: 27430154    Free PMC article.
ST6GALNAC5 Expression Decreases the Interactions between Breast Cancer Cells and the Human Blood-Brain Barrier.
Aurore Drolez, Elodie Vandenhaute, +7 authors, Caroline Mysiorek.
Int J Mol Sci, 2016 Aug 17; 17(8). PMID: 27529215    Free PMC article.
Targeted Therapies for Brain Metastases from Breast Cancer.
Vyshak Alva Venur, José Pablo Leone.
Int J Mol Sci, 2016 Sep 21; 17(9). PMID: 27649142    Free PMC article.
Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry.
Elena Laakmann, Isabell Witzel, +11 authors, Volkmar Mueller.
Int J Mol Sci, 2016 Sep 27; 17(10). PMID: 27669228    Free PMC article.
PTEN mediates the cross talk between breast and glial cells in brain metastases leading to rapid disease progression.
Ina Hohensee, Han-Ning Chuang, +13 authors, Harriet Wikman.
Oncotarget, 2016 Dec 23; 8(4). PMID: 28008153    Free PMC article.
Breast Cancer Brain Metastases: Clonal Evolution in Clinical Context.
Jodi M Saunus, Amy E McCart Reed, Zhun Leong Lim, Sunil R Lakhani.
Int J Mol Sci, 2017 Jan 19; 18(1). PMID: 28098771    Free PMC article.
Targeted Treatment of Brain Metastases.
Nicole Shonka, Vyshak Alva Venur, Manmeet S Ahluwalia.
Curr Neurol Neurosci Rep, 2017 Mar 23; 17(4). PMID: 28326470
Impact of molecular subtypes on metastatic breast cancer patients: a SEER population-based study.
Yue Gong, Yi-Rong Liu, +2 authors, Zhi-Ming Shao.
Sci Rep, 2017 Mar 28; 7. PMID: 28345619    Free PMC article.
Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial.
Javier Cortés, Hope S Rugo, +16 authors, Joyce O'Shaughnessy.
Breast Cancer Res Treat, 2017 Jun 15; 165(2). PMID: 28612225    Free PMC article.
Systemic Treatment Options for HER2-Positive Breast Cancer Patients with Brain Metastases beyond Trastuzumab: A Literature Review.
Elena Laakmann, Volkmar Müller, Marcus Schmidt, Isabell Witzel.
Breast Care (Basel), 2017 Aug 09; 12(3). PMID: 28785185    Free PMC article.
Mystery of the brain metastatic disease in breast cancer patients: improved patient stratification, disease prediction and targeted prevention on the horizon?
Jiri Polivka, Milena Kralickova, +3 authors, Olga Golubnitschaja.
EPMA J, 2017 Aug 22; 8(2). PMID: 28824737    Free PMC article.
CD271 determines migratory properties of melanoma cells.
Josefine Radke, Florian Roßner, Torben Redmer.
Sci Rep, 2017 Aug 31; 7(1). PMID: 28852061    Free PMC article.
Lattice light sheet imaging of membrane nanotubes between human breast cancer cells in culture and in brain metastases.
Ian Parker, Katrina T Evans, +2 authors, Ian F Smith.
Sci Rep, 2017 Sep 10; 7(1). PMID: 28887508    Free PMC article.
Metabolic advantages and vulnerabilities in brain metastases.
Alexandra K Ciminera, Rahul Jandial, John Termini.
Clin Exp Metastasis, 2017 Oct 25; 34(6-7). PMID: 29063238    Free PMC article.
Trastuzumab distribution in an in-vivo and in-vitro model of brain metastases of breast cancer.
Tori B Terrell-Hall, Mohamed Ismail Nounou, +2 authors, Paul R Lockman.
Oncotarget, 2017 Nov 16; 8(48). PMID: 29137378    Free PMC article.
Comprehensive molecular biomarker identification in breast cancer brain metastases.
Hans-Juergen Schulten, Mohammed Bangash, +11 authors, Mohammed H Al-Qahtani.
J Transl Med, 2017 Dec 31; 15(1). PMID: 29287594    Free PMC article.
Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis.
Thaiz F Borin, Kartik Angara, +2 authors, Ali S Arbab.
Int J Mol Sci, 2018 Jan 03; 18(12). PMID: 29292756    Free PMC article.
The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence.
Sara Jansson, Kristina Aaltonen, +4 authors, Lisa Rydén.
Breast Cancer Res Treat, 2018 Jan 31; 169(2). PMID: 29380207    Free PMC article.
Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy - an illustration with firsthand examples.
Rui Xue Zhang, Jason Li, +7 authors, Xiao Yu Wu.
Acta Pharmacol Sin, 2018 Apr 27; 39(5). PMID: 29698389    Free PMC article.
Organotropism: new insights into molecular mechanisms of breast cancer metastasis.
Wenjing Chen, Andrew D Hoffmann, Huiping Liu, Xia Liu.
NPJ Precis Oncol, 2018 Jun 07; 2(1). PMID: 29872722    Free PMC article.
Highly Cited. Review.
DZ-2384 has a superior preclinical profile to taxanes for the treatment of triple-negative breast cancer and is synergistic with anti-CTLA-4 immunotherapy.
Cynthia Bernier, Ahmed Soliman, +7 authors, Anne Roulston.
Anticancer Drugs, 2018 Jun 08; 29(8). PMID: 29878901    Free PMC article.
Therapy of breast cancer brain metastases: challenges, emerging treatments and perspectives.
Nuria Kotecki, Florence Lefranc, Daniel Devriendt, Ahmad Awada.
Ther Adv Med Oncol, 2018 Jul 07; 10. PMID: 29977353    Free PMC article.
Global DNA demethylation as an epigenetic marker of human brain metastases.
Anna-Maria Barciszewska.
Biosci Rep, 2018 Sep 27; 38(5). PMID: 30254100    Free PMC article.
Targeting the PI3K/Akt/mTOR pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases.
Franziska Maria Ippen, Julia Katharina Grosch, +12 authors, Priscilla Kaliopi Brastianos.
Neuro Oncol, 2019 Jun 08; 21(11). PMID: 31173106    Free PMC article.
Impact of Docetaxel on blood-brain barrier function and formation of breast cancer brain metastases.
Simon Bernatz, Elena I Ilina, +13 authors, Michel Mittelbronn.
J Exp Clin Cancer Res, 2019 Oct 31; 38(1). PMID: 31665089    Free PMC article.
Evaluating Magnetic Resonance Spectroscopy as a Tool for Monitoring Therapeutic Response of Whole Brain Radiotherapy in a Mouse Model for Breast-to-Brain Metastasis.
Woon Hyung Chae, Katja Niesel, +8 authors, Lisa Sevenich.
Front Oncol, 2019 Dec 13; 9. PMID: 31828043    Free PMC article.
Tumor microenvironment differences between primary tumor and brain metastases.
Bernardo Cacho-Díaz, Donovan R García-Botello, +3 authors, Luis Alonso Herrera-Montalvo.
J Transl Med, 2020 Jan 05; 18(1). PMID: 31900168    Free PMC article.
Long-term complete response to intrathecal trastuzumab in a patient with leptomeningeal carcinomatosis due to her2- overexpressing breast cancer: Case report.
Francisco José Valdivia García, Natalia Palazón Carrión, Luis de la Cruz-Merino.
Medicine (Baltimore), 2020 Jan 03; 99(1). PMID: 31895768    Free PMC article.
Decreased nonspecific adhesivity, receptor-targeted therapeutic nanoparticles for primary and metastatic breast cancer.
Jimena G Dancy, Aniket S Wadajkar, +8 authors, Anthony J Kim.
Sci Adv, 2020 Jan 31; 6(3). PMID: 31998833    Free PMC article.
microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy.
Ranjana K Kanchan, Jawed A Siddiqui, +2 authors, Mohd W Nasser.
Mol Cancer, 2020 Feb 16; 19(1). PMID: 32059676    Free PMC article.
Astrocytes from the brain microenvironment alter migration and morphology of metastatic breast cancer cells.
Marina A Shumakovich, Caitlin P Mencio, +3 authors, Kimberly M Stroka.
FASEB J, 2017 Nov 01; 31(11). PMID: 32083386    Free PMC article.
Using an in-vivo syngeneic spontaneous metastasis model identifies ID2 as a promoter of breast cancer colonisation in the brain.
Magdalena Kijewska, Carmen Viski, +5 authors, Clare M Isacke.
Breast Cancer Res, 2019 Jan 16; 21(1). PMID: 30642388    Free PMC article.
The Dual PI3K/mTOR Pathway Inhibitor GDC-0084 Achieves Antitumor Activity in PIK3CA-Mutant Breast Cancer Brain Metastases.
Franziska M Ippen, Christopher A Alvarez-Breckenridge, +14 authors, Priscilla K Brastianos.
Clin Cancer Res, 2019 Feb 24; 25(11). PMID: 30796030    Free PMC article.
Clonality of circulating tumor cells in breast cancer brain metastasis patients.
Carlotta Riebensahm, Simon A Joosse, +16 authors, Harriet Wikman.
Breast Cancer Res, 2019 Sep 05; 21(1). PMID: 31481116    Free PMC article.
Improving CNS Delivery to Brain Metastases by Blood-Tumor Barrier Disruption.
Samuel A Sprowls, Tasneem A Arsiwala, +4 authors, Paul R Lockman.
Trends Cancer, 2019 Aug 20; 5(8). PMID: 31421906    Free PMC article.
Metastatic Heterogeneity of Breast Cancer: Companion and Theranostic Approach in Nuclear Medicine.
Christopher Montemagno, Gilles Pagès.
Cancers (Basel), 2020 Apr 03; 12(4). PMID: 32235331    Free PMC article.
GRP94 promotes brain metastasis by engaging pro-survival autophagy.
Naiara Santana-Codina, Laia Muixí, +11 authors, Angels Sierra.
Neuro Oncol, 2019 Oct 23; 22(5). PMID: 31637425    Free PMC article.
Evolving treatment strategies of brain metastases from breast cancer: current status and future direction.
Jae Sik Kim, In Ah Kim.
Ther Adv Med Oncol, 2020 Jul 09; 12. PMID: 32636942    Free PMC article.
Involvement of Kallikrein-Related Peptidases in Nervous System Disorders.
Cinthia Mella, Carlos D Figueroa, Carola Otth, Pamela Ehrenfeld.
Front Cell Neurosci, 2020 Jul 14; 14. PMID: 32655372    Free PMC article.
ALCAM contributes to brain metastasis formation in non-small-cell lung cancer through interaction with the vascular endothelium.
Justine Münsterberg, Desirée Loreth, +23 authors, Harriet Wikman.
Neuro Oncol, 2020 Feb 18; 22(7). PMID: 32064501    Free PMC article.
Survival outcomes of breast cancer patients with brain metastases: A multicenter retrospective study in Korea (KROG 16-12).
Jae Sik Kim, Kyubo Kim, +22 authors, In Ah Kim.
Breast, 2019 Nov 05; 49. PMID: 31677532    Free PMC article.
AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2019.
Marc Thill, Christian Jackisch, +42 authors, Nina Ditsch.
Breast Care (Basel), 2019 Sep 29; 14(4). PMID: 31558898    Free PMC article.
Proliferative Classification of Intracranially Injected HER2-positive Breast Cancer Cell Lines.
Yuka Kuroiwa, Jun Nakayama, +3 authors, Kentaro Semba.
Cancers (Basel), 2020 Jul 10; 12(7). PMID: 32640677    Free PMC article.
Heterogeneity and vascular permeability of breast cancer brain metastases.
Maria V Babak, Michael R Zalutsky, Irina V Balyasnikova.
Cancer Lett, 2020 Jun 21; 489. PMID: 32561415    Free PMC article.
Genomic landscape of the immune microenvironments of brain metastases in breast cancer.
Wei-Cheng Lu, Hui Xie, +3 authors, An-Hua Wu.
J Transl Med, 2020 Sep 02; 18(1). PMID: 32867782    Free PMC article.
miRNAs in Health and Disease: A Focus on the Breast Cancer Metastatic Cascade towards the Brain.
Marta Sereno, Mafalda Videira, +2 authors, Maria Alexandra Brito.
Cells, 2020 Aug 01; 9(8). PMID: 32731349    Free PMC article.
ATTAIN: Phase III study of etirinotecan pegol versus treatment of physician's choice in patients with metastatic breast cancer and brain metastases.
Debu Tripathy, Sara M Tolaney, +9 authors, Javier Cortés.
Future Oncol, 2019 May 11; 15(19). PMID: 31074641    Free PMC article.
Aberrant HDAC3 expression correlates with brain metastasis in breast cancer patients.
Li Ma, Lisha Qi, +8 authors, Wenliang Li.
Thorac Cancer, 2020 Jul 21; 11(9). PMID: 32686908    Free PMC article.
Circulating MicroRNAs and Blood-Brain-Barrier Function in Breast Cancer Metastasis.
Carolin J Curtaz, Constanze Schmitt, +3 authors, Malgorzata Burek.
Curr Pharm Des, 2020 Mar 17; 26(13). PMID: 32175838    Free PMC article.
Local and systemic treatment for HER2-positive breast cancer with brain metastases: a comprehensive review.
Wing-Lok Chan, Tai-Chung Lam, +3 authors, Lai-Wan Dora Kwong.
Ther Adv Med Oncol, 2020 Sep 26; 12. PMID: 32973930    Free PMC article.
Neural Network Deconvolution Method for Resolving Pathway-Level Progression of Tumor Clonal Expression Programs With Application to Breast Cancer Brain Metastases.
Yifeng Tao, Haoyun Lei, +2 authors, Russell Schwartz.
Front Physiol, 2020 Oct 06; 11. PMID: 33013452    Free PMC article.
Clinicopathologic significance of nuclear HER4 and phospho-YAP(S127) in human breast cancers and matching brain metastases.
Priyakshi Kalita-de Croft, Malcolm Lim, +8 authors, Jodi M Saunus.
Ther Adv Med Oncol, 2020 Oct 06; 12. PMID: 33014146    Free PMC article.
Metastatic brain tumors respond favorably to pyrotinib in a HER2-positive breast cancer following failure using trastuzumab.
Jing-Hao Yao, Zong-Yu Xie, +3 authors, Yan Yang.
Am J Transl Res, 2020 Oct 13; 12(9). PMID: 33042466    Free PMC article.
A view on the landscape of breast cancer brain metastases.
Rachna Malani.
CNS Oncol, 2020 Sep 30; 9(3). PMID: 32990026    Free PMC article.
Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases.
Elena Laakmann, Isabell Witzel, +17 authors, Volkmar Müller.
Cancers (Basel), 2020 Oct 02; 12(10). PMID: 32998430    Free PMC article.
BR-BCSC Signature: The Cancer Stem Cell Profile Enriched in Brain Metastases that Predicts a Worse Prognosis in Lymph Node-Positive Breast Cancer.
Maria Rita Dionísio, André F Vieira, +15 authors, Joana Paredes.
Cells, 2020 Nov 14; 9(11). PMID: 33182375    Free PMC article.
CDK 4/6 inhibitors and stereotactic radiation in the management of hormone receptor positive breast cancer brain metastases.
Nicholas B Figura, Thrisha K Potluri, +12 authors, Kamran A Ahmed.
J Neurooncol, 2019 Aug 11; 144(3). PMID: 31399935
A metastasis map of human cancer cell lines.
Xin Jin, Zelalem Demere, +16 authors, Todd R Golub.
Nature, 2020 Dec 11; 588(7837). PMID: 33299191
Autophagy-mediated tumor cell survival and progression of breast cancer metastasis to the brain.
Aparna Maiti, Nitai C Hait.
J Cancer, 2021 Jan 15; 12(4). PMID: 33442395    Free PMC article.
The Metabolic Mechanisms of Breast Cancer Metastasis.
Lingling Wang, Shizhen Zhang, Xiaochen Wang.
Front Oncol, 2021 Jan 26; 10. PMID: 33489906    Free PMC article.
Predicting Prognosis of Breast Cancer Patients with Brain Metastases in the BMBC Registry-Comparison of Three Different GPA Prognostic Scores.
Kerstin Riecke, Volkmar Müller, +16 authors, Isabell Witzel.
Cancers (Basel), 2021 Mar 07; 13(4). PMID: 33671376    Free PMC article.
Factors affecting time to brain metastases for stage 2 and 3 breast cancer patients: A large single-institutional analysis with potential screening implications.
Toni Q Cao, Karan Dixit, Cesar Santa-Maria, Priya Kumthekar.
Neurooncol Adv, 2021 Mar 20; 3(1). PMID: 33738445    Free PMC article.
Breast cancer subtype predicts clinical outcomes after stereotactic radiation for brain metastases.
Matthew N Mills, Chetna Thawani, +12 authors, Kamran A Ahmed.
J Neurooncol, 2021 Mar 21; 152(3). PMID: 33742358
Sex steroid hormone function in the brain niche: Implications for brain metastatic colonization and progression.
María J Contreras-Zárate, Diana M Cittelly.
Cancer Rep (Hoboken), 2020 Dec 23;. PMID: 33350105    Free PMC article.
Inhibition of the Growth of Breast Cancer-Associated Brain Tumors by the Osteocyte-Derived Conditioned Medium.
Tomohiko Sano, Xun Sun, +9 authors, Hiroki Yokota.
Cancers (Basel), 2021 Apr 04; 13(5). PMID: 33802279    Free PMC article.
Ca2+ Signaling as the Untact Mode during Signaling in Metastatic Breast Cancer.
Dongun Lee, Jeong Hee Hong.
Cancers (Basel), 2021 Apr 04; 13(6). PMID: 33806911    Free PMC article.
Identification of markers associated with brain metastasis from breast cancer through bioinformatics analysis and verification in clinical samples.
Yongchang Gao, Jianjing Liu, Xiaolong Qian, Xianghui He.
Gland Surg, 2021 Apr 13; 10(3). PMID: 33842237    Free PMC article.
Th1 cytokine interferon gamma improves response in HER2 breast cancer by modulating the ubiquitin proteasomal pathway.
Yongsheng Jia, Krithika N Kodumudi, +17 authors, Brian J Czerniecki.
Mol Ther, 2021 Jan 08; 29(4). PMID: 33412308    Free PMC article.
Mechanical tibial loading remotely suppresses brain tumors by dopamine-mediated downregulation of CCN4.
Yao Fan, Rongrong Zha, +17 authors, Hiroki Yokota.
Bone Res, 2021 May 26; 9(1). PMID: 34031366    Free PMC article.