Table of Contents Author Guidelines Submit a Manuscript
Genetics Research International
Volume 2011, Article ID 219189, 9 pages
http://dx.doi.org/10.4061/2011/219189
Review Article

Molecular Aspects of Breast Cancer Metastasis to the Brain

1UQ Centre for Clinical Research, The University of Queensland, Herston, QLD 4029, Australia
2School of Medicine, The University of Queensland, Herston, QLD 4029, Australia
3Pathology Queensland, The Royal Brisbane and Women’s Hospital, Herston, QLD 4029, Australia

Received 30 April 2011; Revised 15 July 2011; Accepted 14 August 2011

Academic Editor: Sergio Roa

Copyright © 2011 Jodi M. Saunus et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. Paget, “The distribution of secondary growths in cancer of the breast. 1889,” Cancer and Metastasis Reviews, vol. 8, no. 2, pp. 98–101, 1989. View at Google Scholar · View at Scopus
  2. Y. Tsukada, A. Fouad, J. W. Pickren, and W. W. Lane, “Central nervous system metastasis from breast carcinoma. Autopsy study,” Cancer, vol. 52, no. 12, pp. 2349–2354, 1983. View at Google Scholar · View at Scopus
  3. W. Boogerd, V. W. Vos, A. A. M. Hart, and G. Baris, “Brain metastases in breast cancer; natural history, prognostic factors and outcome,” Journal of Neuro-Oncology, vol. 15, no. 2, pp. 165–174, 1993. View at Google Scholar · View at Scopus
  4. R. N. Kaplan, R. D. Riba, S. Zacharoulis et al., “VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche,” Nature, vol. 438, no. 7069, pp. 820–827, 2005. View at Publisher · View at Google Scholar · View at Scopus
  5. M. R. Dawson, D. G. Duda, D. Fukumura, and R. K. Jain, “VEGFR1-activity-independent metastasis formation,” Nature, vol. 461, no. 7262, pp. E4–E5, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. K. J. Luzzi, I. C. MacDonald, E. E. Schmidt et al., “Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases,” American Journal of Pathology, vol. 153, no. 3, pp. 865–873, 1998. View at Google Scholar · View at Scopus
  7. R. L. Vessella, K. Pantel, and S. Mohla, “Tumor cell dormancy: an NCI workshop report,” Cancer Biology and Therapy, vol. 6, no. 9, pp. 1496–1504, 2007. View at Google Scholar · View at Scopus
  8. F. Li, B. Tiede, J. Massagué, and Y. Kang, “Beyond tumorigenesis: cancer stem cells in metastasis,” Cell Research, vol. 17, no. 1, pp. 3–14, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. A. L. Allana, S. A. Vantyghem, A. B. Tuck, and A. F. Chambers, “Tumor dormancy and cancer stem cells: implications for the biology and treatment of breast cancer metastasis,” Breast Disease, vol. 26, no. 1, pp. 87–98, 2006. View at Google Scholar · View at Scopus
  10. L. A. Mina and G. W. Sledge Jr., “Rethinking the metastatic cascade as a therapeutic target,” Nature Reviews Clinical Oncology, vol. 8, no. 6, pp. 325–332, 2011. View at Publisher · View at Google Scholar
  11. D. X. Nguyen, P. D. Bos, and J. Massagué, “Metastasis: from dissemination to organ-specific colonization,” Nature Reviews Cancer, vol. 9, no. 4, pp. 274–284, 2009. View at Publisher · View at Google Scholar · View at Scopus
  12. L. Da Silva, P. T. Simpson, C. E. Smart et al., “HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer,” Breast Cancer Research, vol. 12, no. 4, article R46, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. B. Weigelt, A. M. Glas, L. F. A. Wessels, A. T. Witteveen, J. L. Peterse, and L. J. Van'T Veer, “Gene expression profiles of primary breast tumors maintained in distant metastases,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 26, pp. 15901–15905, 2003. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Vecchi, S. Confalonieri, P. Nuciforo et al., “Breast cancer metastases are molecularly distinct from their primary tumors,” Oncogene, vol. 27, no. 15, pp. 2148–2158, 2008. View at Publisher · View at Google Scholar · View at Scopus
  15. S. P. Shah, R. D. Morin, J. Khattra et al., “Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution,” Nature, vol. 461, no. 7265, pp. 809–813, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Yachida, S. Jones, I. Bozic et al., “Distant metastasis occurs late during the genetic evolution of pancreatic cancer,” Nature, vol. 467, no. 7319, pp. 1114–1117, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. Y. Urano, T. Fukushima, S. Kitamura, H. Mori, K. Baba, and S. Aizawa, “Statistical studies on metastasis of breast cancer and cancer metastasis to the breast,” Gan No Rinsho, vol. Suppl, pp. 205–223, 1986. View at Google Scholar · View at Scopus
  18. N. U. Lin, J. R. Bellon, and E. P. Winer, “CNS metastases in breast cancer,” Journal of Clinical Oncology, vol. 22, no. 17, pp. 3608–3617, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. Y. L. Tham, K. Sexton, R. Kramer, S. Hilsenbeck, and R. Elledge, “Primary breast cancer phenotypes associated with propensity for central nervous system metastases,” Cancer, vol. 107, no. 4, pp. 696–704, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. L. G. Fulford, J. S. Reis-Filho, K. Ryder et al., “Basal-like grade III invasive ductal carcinoma of the breast: patterns of metastasis and long-term survival,” Breast Cancer Research, vol. 9, no. 1, article R4, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Gaedcke, F. Traub, S. Milde et al., “Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer,” Modern Pathology, vol. 20, no. 8, pp. 864–870, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. D. G. Hicks, S. M. Short, N. L. Prescott et al., “Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin CK5/6, and overexpress HER2 or EGFR,” American Journal of Surgical Pathology, vol. 30, no. 9, pp. 1097–1104, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. P. K. Sneed, D. A. Larson, and W. M. Wara, “Radiotherapy for cerebral metastases,” Neurosurgery Clinics of North America, vol. 7, no. 3, pp. 505–515, 1996. View at Google Scholar
  24. Y. H. Park, M. J. Park, S. H. Ji et al., “Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients,” British Journal of Cancer, vol. 100, no. 6, pp. 894–900, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. C. M. Perou, T. Sørile, M. B. Eisen et al., “Molecular portraits of human breast tumours,” Nature, vol. 406, no. 6797, pp. 747–752, 2000. View at Publisher · View at Google Scholar · View at Scopus
  26. T. Sørlie, C. M. Perou, R. Tibshirani et al., “Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 19, pp. 10869–10874, 2001. View at Publisher · View at Google Scholar · View at Scopus
  27. L. Da Silva, C. Clarke, and S. R. Lakhani, “Demystifying basal-like breast carcinomas,” Journal of Clinical Pathology, vol. 60, no. 12, pp. 1328–1332, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. E. A. Rakha, J. S. Reis-Filho, and I. O. Ellis, “Basal-like breast cancer: a critical review,” Journal of Clinical Oncology, vol. 26, no. 15, pp. 2568–2581, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. L. Albiges, F. André, C. Balleyguier, G. Gomez-Abuin, A. Chompret, and S. Delaloge, “Spectrum of breast cancer metastasis in BRCA1 mutation carriers: highly increased incidence of brain metastases,” Annals of Oncology, vol. 16, no. 11, pp. 1846–1847, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. N. U. Lin and E. P. Winer, “Brain metastases: the HER2 paradigm,” Clinical Cancer Research, vol. 13, no. 6, pp. 1648–1655, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. H. Kennecke, R. Yerushalmi, R. Woods et al., “Metastatic behavior of breast cancer subtypes,” Journal of Clinical Oncology, vol. 28, no. 20, pp. 3271–3277, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. D. Khaitan, U. T. Sankpal, B. Weksler et al., “Role of KCNMA1 gene in breast cancer invasion and metastasis to brain,” BMC Cancer, vol. 9, article 258, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. I. Nishizuka, T. Ishikawa, Y. Hamaguchi et al., “Analysis of gene expression involved in brain metastasis from breast cancer using cDNA microarray,” Breast Cancer, vol. 9, no. 1, pp. 26–32, 2002. View at Google Scholar · View at Scopus
  34. P. D. Bos, X. H. F. Zhang, C. Nadal et al., “Genes that mediate breast cancer metastasis to the brain,” Nature, vol. 459, no. 7249, pp. 1005–1009, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. B. C. Lee, T. H. Lee, S. Avraham, and H. K. Avraham, “Involvement of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1α in breast cancer cell migration through human brain microvascular endothelial cells,” Molecular Cancer Research, vol. 2, no. 6, pp. 327–338, 2004. View at Google Scholar · View at Scopus
  36. O. Mendes, H. T. Kim, and G. Stoica, “Expression of MMP2, MMP9 and MMP3 in breast cancer brain metastasis in a rat model,” Clinical and Experimental Metastasis, vol. 22, no. 3, pp. 237–246, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. B. C. Schmid, G. A. Rezniczek, G. Fabjani, T. Yoneda, S. Leodolter, and R. Zeillinger, “The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells,” Breast Cancer Research and Treatment, vol. 106, no. 3, pp. 333–342, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. W.-T. Chiu, H.-T. Lee, F.-J. Huang et al., “Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by Stat3 inhibition,” Cancer Research, vol. 71, no. 14, pp. 4932–4943, 2011. View at Publisher · View at Google Scholar
  39. D. Palmieri, J. L. Bronder, J. M. Herring et al., “Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain,” Cancer Research, vol. 67, no. 9, pp. 4190–4198, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. L. S. Kim, S. Huang, W. Lu, D. C. Lev, and J. E. Price, “Vascular endothelial growth factor expression promotes the growth of breast cancer brain metastases in nude mice,” Clinical and Experimental Metastasis, vol. 21, no. 2, pp. 107–118, 2004. View at Publisher · View at Google Scholar · View at Scopus
  41. C. E. Geyer, J. Forster, D. Lindquist et al., “Lapatinib plus capecitabine for HER2-positive advanced breast cancer,” New England Journal of Medicine, vol. 355, no. 26, pp. 2733–2743, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. I. J. Fidler, “The role of the organ microenvironment in brain metastasis,” Seminars in Cancer Biology, vol. 21, no. 2, pp. 107–112, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. I. J. Fidler, K. Balasubramanian, Q. Lin, S. W. Kim, and S.-J. Kim, “The brain microenvironment and cancer metastasis,” Molecules and Cells, vol. 30, no. 2, pp. 93–98, 2010. View at Publisher · View at Google Scholar
  44. L. Ding, M. J. Ellis, S. Li et al., “Genome remodelling in a basal-like breast cancer metastasis and xenograft,” Nature, vol. 464, no. 7291, pp. 999–1005, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. O. Mendes, H. T. Kim, G. Lungu, and G. Stoica, “MMP2 role in breast cancer brain metastasis development and its regulation by TIMP2 and ERK1/2,” Clinical and Experimental Metastasis, vol. 24, no. 5, pp. 341–351, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. D. P. Fitzgerald, D. Palmieri, E. Hua et al., “Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization,” Clinical and Experimental Metastasis, vol. 25, no. 7, pp. 799–810, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. A. Sierra, J. E. Price, M. García-Ramirez, O. Méndez, L. López, and A. Fabra, “Astrocyte-derived cytokines contribute to the metastatic brain specificity of breast cancer cells,” Laboratory Investigation, vol. 77, no. 4, pp. 357–368, 1997. View at Google Scholar · View at Scopus
  48. B. Gril, D. Palmieri, J. L. Bronder et al., “Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain,” Journal of the National Cancer Institute, vol. 100, no. 15, pp. 1092–1103, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. D. Palmieri, D. Fitzgerald, S. M. Shreeve et al., “Analyses of resected human brain metastases of breast cancer reveal the association between up-regulation of hexokinase 2 and poor prognosis,” Molecular Cancer Research, vol. 7, no. 9, pp. 1438–1445, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. A. J. Law, C. Shannon Weickert, T. M. Hyde, J. E. Kleinman, and P. J. Harrison, “Neuregulin-1 (NRG-1) mRNA and protein in the adult human brain,” Neuroscience, vol. 127, no. 1, pp. 125–136, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. G. L. Wang and G. L. Semenza, “General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 9, pp. 4304–4308, 1993. View at Google Scholar · View at Scopus
  52. M. Sun, C. Behrens, L. Feng et al., “HER family receptor abnormalities in lung cancer brain metastases and corresponding primary tumors,” Clinical Cancer Research, vol. 15, no. 15, pp. 4829–4837, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. L. Zhang, P. S. Sullivan, J. C. Goodman, P. H. Gunaratne, and D. Marchetti, “MicroRNA-1258 suppresses breast cancer brain metastasis by targeting heparanase,” Cancer Research, vol. 71, no. 3, pp. 645–654, 2011. View at Publisher · View at Google Scholar
  54. N. U. Lin, V. Diéras, D. Paul et al., “Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer,” Clinical Cancer Research, vol. 15, no. 4, pp. 1452–1459, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. S.-J. Kim, J.-S. Kim, E. S. Park et al., “Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy,” Neoplasia, vol. 13, no. 3, pp. 286–298, 2011. View at Publisher · View at Google Scholar
  56. S. Ostrand-Rosenberg, “Mouse SaI sarcoma tumor model,” Current Protocols in Immunology, vol. Chapter 20, p. Unit 20.3, 2001. View at Google Scholar
  57. T. Yoneda, P. J. Williams, T. Hiraga, M. Niewolna, and R. Nishimura, “A bone-seeking clone exhibits different biological properties from the MDA-MB-231 parental human breast cancer cells and a brain-seeking clone in vivo and in vitro,” Journal of Bone and Mineral Research, vol. 16, no. 8, pp. 1486–1495, 2001. View at Google Scholar · View at Scopus
  58. H. J. Burstein, I. Kuter, S. M. Campos et al., “Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer,” Journal of Clinical Oncology, vol. 19, no. 10, pp. 2722–2730, 2001. View at Google Scholar · View at Scopus
  59. J. Baselga, K. A. Gelmon, S. Verma et al., “Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy,” Journal of Clinical Oncology, vol. 28, no. 7, pp. 1138–1144, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. H. J. Burstein, Y. Sun, L. Y. Dirix et al., “Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer,” Journal of Clinical Oncology, vol. 28, no. 8, pp. 1301–1307, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. K. Miller, M. Wang, J. Gralow et al., “Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer,” New England Journal of Medicine, vol. 357, no. 26, pp. 2666–2676, 2007. View at Publisher · View at Google Scholar · View at Scopus
  62. B. Escudier, T. Eisen, W. M. Stadler et al., “Sorafenib in advanced clear-cell renal-cell carcinoma,” New England Journal of Medicine, vol. 356, no. 2, pp. 125–134, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. T. K. Choueiri, “Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors,” Current Opinion in Investigational Drugs, vol. 9, no. 6, pp. 658–671, 2008. View at Google Scholar · View at Scopus
  64. R. Addeo and M. Caraglia, “The oral tyrosine kinase inhibitors lapatinib and sunitinib: new opportunities for the treatment of brain metastases from breast cancer?” Expert Review of Anticancer Therapy, vol. 11, no. 2, pp. 139–142, 2011. View at Publisher · View at Google Scholar
  65. F. Petrelli, M. Cabiddu, M. Carpo, M. Ghilardi, and S. Barni, “Progression of intramedullary metastasis during perioperative cessation of sunitinib,” Nature Reviews Urology, vol. 7, no. 11, pp. 634–637, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. R. J. Motzer, T. E. Hutson, P. Tomczak et al., “Sunitinib versus interferon alfa in metastatic renal-cell carcinoma,” New England Journal of Medicine, vol. 356, no. 2, pp. 115–124, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. T. E. Hutson, I. D. Davis, J. P. H. Machiels et al., “Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma,” Journal of Clinical Oncology, vol. 28, no. 3, pp. 475–480, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. N. U. Lin, L. A. Carey, M. C. Liu et al., “Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer,” Journal of Clinical Oncology, vol. 26, no. 12, pp. 1993–1999, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. U. M. Vogl, M. Bojic, W. Lamm et al., “Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma,” BMC Cancer, vol. 10, article 480, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. A. Grigoriadis, O. L. Caballero, K. S. Hoek et al., “CT-X antigen expression in human breast cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 32, pp. 13493–13498, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. W. Lu, C. D. Bucana, and A. J. Schroit, “Pathogenesis and vascular integrity of breast cancer brain metastasis,” International Journal of Cancer, vol. 120, no. 5, pp. 1023–1026, 2007. View at Publisher · View at Google Scholar · View at Scopus