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Optimal Management of Brain Metastases from Breast Cancer

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Abstract

The incidence of brain metastases (BM) in breast cancer patients has increased over the last decade, presumably due to advances in systemic treatment. Today, breast cancer is the second most common cause of BM among all solid malignancies, second only to lung cancer; furthermore, it is the most common cause of leptomeningeal carcinomatosis. The HER2-positive subtype was consistently shown to have a higher risk for BM as compared with HER2-negative disease. More recently, however, it was shown that a similar incidence exists in triple-negative tumours. Local treatment options, radiotherapy and neurosurgical resection, remain the mainstay of therapy for BM. While some studies have suggested a direct effect of conventional chemotherapy on BM, the main beneficial aspect of systemic treatment is rather due to control of non-CNS systemic disease. Importantly, in patients with HER2-positive breast cancer receiving HER2-targeted therapy after local treatment for BM, superior survival outcomes were reported. Leptomeningeal carcinomatosis has a dismal prognosis. Survival with whole brain radiotherapy alone remains short and the potential additional benefit of intrathecal chemotherapy is still disputed. According to case reports, intrathecal administration of trastuzumab appears to be a promising strategy in patients with HER2-positive leptomeningeal carcinomatosis. In conclusion, while the outcome of breast cancer patients with BM has improved especially in the HER2-positive subtype, the prognosis for the majority of patients remains poor. Therefore, development of novel systemic treatment options offering activity within the brain is urgently warranted. Novel insights into the pathobiology of BM formation may offer the possibility for targeted drug prophylaxis of CNS involvement in high-risk patients.

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References

  1. Society AC. Global cancer facts and figures (online). http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-027766.pdf. Accessed 24 Nov 2011.

  2. Lee SS, Ahn JH, Kim MK, et al. Brain metastases in breast cancer: prognostic factors and management. Breast Cancer Res Treat. 2008;111(3):523–30.

    Article  PubMed  Google Scholar 

  3. Tsukada Y, Fouad A, Pickren JW, et al. Central nervous system metastasis from breast carcinoma: autopsy study. Cancer. 1983;52(12):2349–54.

    Article  PubMed  CAS  Google Scholar 

  4. Weil RJ, Palmieri DC, Bronder JL, et al. Breast cancer metastasis to the central nervous system. Am J Pathol. 2005;167(4):913–20.

    Article  PubMed  CAS  Google Scholar 

  5. Miller KD, Weathers T, Haney LG, et al. Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival. Ann Oncol. 2003;14(7):1072–7.

    Article  PubMed  CAS  Google Scholar 

  6. Lin NU, Bellon JR, Winer EP. CNS metastases in breast cancer. J Clin Oncol. 2004;22(17):3608–17.

    Article  PubMed  Google Scholar 

  7. Evans AJ, James JJ, Cornford EJ, et al. Brain metastases from breast cancer: identification of a high-risk group. Clin Oncol (R Coll Radiol). 2004;16(5):345–9.

    Google Scholar 

  8. Slimane K, Andre F, Delaloge S, et al. Risk factors for brain relapse in patients with metastatic breast cancer. Ann Oncol. 2004;15(11):1640–4.

    Article  PubMed  CAS  Google Scholar 

  9. Gabos Z, Sinha R, Hanson J, et al. Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J Clin Oncol. 2006;24(36):5658–63.

    Article  PubMed  CAS  Google Scholar 

  10. Brufsky AM, Mayer M, Rugo HS, et al. Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res. 2011;17(14):4834–43.

    Article  PubMed  CAS  Google Scholar 

  11. Stemmler HJ, Schmitt M, Willems A, et al. 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. Anticancer Drugs. 2007;18(1):23–8.

    Article  PubMed  CAS  Google Scholar 

  12. Yau T, Swanton C, Chua S, et al. Incidence, pattern and timing of brain metastases among patients with advanced breast cancer treated with trastuzumab. Acta Oncol. 2006;45(2):196–201.

    Article  PubMed  CAS  Google Scholar 

  13. Pestalozzi BC, Zahrieh D, Price KN, et al. Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol. 2006;17(6):935–44.

    Article  PubMed  CAS  Google Scholar 

  14. Konecny GE, Meng YG, Untch M, et al. Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res. 2004;10(5):1706–16.

    Article  PubMed  CAS  Google Scholar 

  15. Palmieri D, Bronder JL, Herring JM, et al. HER-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Res. 2007;67(9):4190–8.

    Article  PubMed  CAS  Google Scholar 

  16. Lin NU, Claus E, Sohl J, et al. Sites of distant recurrence and clinical outcomes in patients with metastatic triple-negative breast cancer: high incidence of central nervous system metastases. Cancer. 2008;113(10):2638–45.

    Article  PubMed  Google Scholar 

  17. Berghoff A, Bago-Horvath Z, De Vries C, et al. Brain metastases free survival differs between breast cancer subtypes. Br J Cancer. 2012;106(3):440–6.

    Article  PubMed  CAS  Google Scholar 

  18. Gaspar L, Scott C, Rotman M, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37(4):745–51.

    Article  PubMed  CAS  Google Scholar 

  19. Sperduto PW, Kased N, Roberge D, et al. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012;30(4):419–25.

    Article  PubMed  Google Scholar 

  20. Sperduto PW, Kased N, Roberge D, et al. Effect of tumor subtype on survival and the graded prognostic assessment for patients with breast cancer and brain metastases. Int J Radiat Oncol Biol Phys. 2012;82(5):2111–7.

    Article  PubMed  Google Scholar 

  21. Weissman DE. Glucocorticoid treatment for brain metastases and epidural spinal cord compression: a review. J Clin Oncol. 1988;6(3):543–51.

    PubMed  CAS  Google Scholar 

  22. Lutterbach J, Bartelt S, Stancu E, et al. Patients with brain metastases: hope for recursive partitioning analysis (RPA) class 3. Radiother Oncol. 2002;63(3):339–45.

    Article  PubMed  Google Scholar 

  23. Broadbent AM, Hruby G, Tin MM, et al. Survival following whole brain radiation treatment for cerebral metastases: an audit of 474 patients. Radiother Oncol. 2004;71(3):259–65.

    Article  PubMed  Google Scholar 

  24. Eichler AF, Loeffler JS. Multidisciplinary management of brain metastases. Oncologist. 2007;12(7):884–98.

    Article  PubMed  CAS  Google Scholar 

  25. Khuntia D, Brown P, Li J, et al. Whole-brain radiotherapy in the management of brain metastasis. J Clin Oncol. 2006;24(8):1295–304.

    Article  PubMed  CAS  Google Scholar 

  26. Mayer M. A patient perspective on brain metastases in breast cancer. Clin Cancer Res. 2007;13(6):1623–4.

    Article  PubMed  Google Scholar 

  27. Kondziolka D, Niranjan A, Flickinger JC, et al. Radiosurgery with or without whole-brain radiotherapy for brain metastases: the patients’ perspective regarding complications. Am J Clin Oncol. 2005;28(2):173–9.

    Article  PubMed  Google Scholar 

  28. Bachelot T, Romieu G, Campone M, et al. LANDSCAPE: an FNCLCC phase II study with lapatinib (L) and capecitabine (C) in patients with brain metastases (BM) from HER2-positive (+) metastatic breast cancer (MBC) before whole-brain radiotherapy (WBR) [abstract]. J Clin Oncol. 2011;29(Suppl. 15):509.

    Google Scholar 

  29. Feyer P, Sautter-Bihl ML, Budach W, et al. DEGRO practical guidelines for palliative radiotherapy of breast cancer patients: brain metastases and leptomeningeal carcinomatosis. Strahlenther Onkol. 2010;186(2):63–9.

    Article  PubMed  Google Scholar 

  30. Vecht CJ, Hovestadt A, Verbiest HB, et al. Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day. Neurology. 1994;44(4):675–80.

    Article  PubMed  CAS  Google Scholar 

  31. Rades D, Panzner A, Dziggel L, et al. Dose-escalation of whole-brain radiotherapy for brain metastasis in patients with a favorable survival prognosis. Cancer. 2012;118(15):3852–9.

    Article  PubMed  Google Scholar 

  32. Nieder C, Nestle U, Niewald M, et al. Accelerated radiotherapy for brain metastases. Radiother Oncol. 1997;45(1):17–22.

    Article  PubMed  CAS  Google Scholar 

  33. 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(5):942–8.

    Article  PubMed  CAS  Google Scholar 

  34. Pease NJ, Edwards A, Moss LJ. Effectiveness of whole brain radiotherapy in the treatment of brain metastases: a systematic review. Palliat Med. 2005;19(4):288–99.

    Article  PubMed  CAS  Google Scholar 

  35. Patil CG, Pricola K, Garg SK, et al. Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. Cochrane Database Syst Rev. 2010;(6):CD006121.

  36. Hendrickson FR, Lee MS, Larson M, et al. The influence of surgery and radiation therapy on patients with brain metastases. Int J Radiat Oncol Biol Phys. 1983;9(5):623–7.

    Article  PubMed  CAS  Google Scholar 

  37. Mut M. Surgical treatment of brain metastasis: a review. Clin Neurol Neurosurg. 2012;114(1):1–8.

    Article  PubMed  Google Scholar 

  38. Rades D, Schild SE. Do patients with a limited number of brain metastases need whole-brain radiotherapy in addition to radiosurgery? Strahlenther Onkol. 2012 Aug; 188 (8): 702-6.

  39. Tsao MN, Lloyd N, Wong RK, et al. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2012;(4):CD003869.

  40. Bartsch R, Berghoff A, Pluschnig U, et al. Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases. Br J Cancer. 2012;106(1):25–31.

    Article  PubMed  CAS  Google Scholar 

  41. Bartsch R, Rottenfusser A, Wenzel C, et al. Trastuzumab prolongs overall survival in patients with brain metastases from HER2 positive breast cancer. J Neurooncol. 2007;85(3):311–7.

    Article  PubMed  CAS  Google Scholar 

  42. Lower EE, Drosick DR, Blau R, et al. Increased rate of brain metastasis with trastuzumab therapy not associated with impaired survival. Clin Breast Cancer. 2003;4(2):114–9.

    Article  PubMed  CAS  Google Scholar 

  43. Kirsch DG, Ledezma CJ, Mathews CS, et al. Survival after brain metastases from breast cancer in the trastuzumab era. J Clin Oncol. 2005;23(9):2114–6 (author reply 2116–7).

    Google Scholar 

  44. Metro G, Foglietta J, Russillo M, et al. Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine. Ann Oncol. 2011;22(3):625–30.

    Article  PubMed  CAS  Google Scholar 

  45. Preusser M, Capper D, Ilhan-Mutlu A, et al. Brain metastases: pathobiology and emerging targeted therapies. Acta Neuropathol. 2012;123(2):205–22.

    Article  PubMed  CAS  Google Scholar 

  46. Front D, Israel O, Kohn S, et al. The blood-tissue barrier of human brain tumors: correlation of scintigraphic and ultrastructural findings: concise communication. J Nucl Med. 1984;25(4):461–5.

    PubMed  CAS  Google Scholar 

  47. Bertossi M, Virgintino D, Maiorano E, et al. Ultrastructural and morphometric investigation of human brain capillaries in normal and peritumoral tissues. Ultrastruct Pathol. 1997;21(1):41–9.

    Google Scholar 

  48. Gerstner ER, Fine RL. Increased permeability of the blood–brain barrier to chemotherapy in metastatic brain tumors: establishing a treatment paradigm. J Clin Oncol. 2007;25(16):2306–12.

    Article  PubMed  Google Scholar 

  49. Zhang RD, Price JE, Fujimaki T, et al. Differential permeability of the blood–brain barrier in experimental brain metastases produced by human neoplasms implanted into nude mice. Am J Pathol. 1992;141(5):1115–24.

    PubMed  CAS  Google Scholar 

  50. Dietrich WD, Busto R, Halley M, et al. The importance of brain temperature in alterations of the blood–brain barrier following cerebral ischemia. J Neuropathol Exp Neurol. 1990;49(5):486–97.

    Article  PubMed  CAS  Google Scholar 

  51. Cordon-Cardo C, O’Brien JP, Boccia J, et al. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J Histochem Cytochem. 1990;38(9):1277–87.

    Article  PubMed  CAS  Google Scholar 

  52. Gallo JM, Li S, Guo P, et al. The effect of P-glycoprotein on paclitaxel brain and brain tumor distribution in mice. Cancer Res. 2003;63(16):5114–7.

    PubMed  CAS  Google Scholar 

  53. Yonemori K, Tsuta K, Ono M, et al. Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neu-positive breast cancer. Cancer. 2010;116(2):302–8.

    Article  PubMed  Google Scholar 

  54. Rosner D, Nemoto T, Lane WW. Chemotherapy induces regression of brain metastases in breast carcinoma. Cancer. 1986;58(4):832–9.

    Article  PubMed  CAS  Google Scholar 

  55. Boogerd W, Dalesio O, Bais EM, et al. Response of brain metastases from breast cancer to systemic chemotherapy. Cancer. 1992;69(4):972–80.

    Article  PubMed  CAS  Google Scholar 

  56. Ekenel M, Hormigo AM, Peak S, et al. Capecitabine therapy of central nervous system metastases from breast cancer. J Neurooncol. 2007;85(2):223–7.

    Article  PubMed  CAS  Google Scholar 

  57. Fabi A, Vidiri A, Ferretti G, et al. Dramatic regression of multiple brain metastases from breast cancer with capecitabine: another arrow at the bow? Cancer Invest. 2006;24(4):466–8.

    Article  PubMed  CAS  Google Scholar 

  58. Anders C, Adamo B, Walsh M, et al. Pharmacokinetic disposition of PEGylated liposomal doxorubicin compared with non-liposomal doxorubicin in an intracranial breast cancer murine model (abstract). Cancer Res. 2011;71(Suppl. 24):P4-17-04. 34th annual CTRC-AACR San Antonio breast cancer symposium; 6–10 Dec 2011, San Antonio (TX).

  59. Lockman PR, Mittapalli RK, Taskar KS, et al. Heterogeneous blood–tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer. Clin Cancer Res. 2010;16(23):5664–78.

    Article  PubMed  CAS  Google Scholar 

  60. Newlands ES, Stevens MF, Wedge SR, et al. Temozolomide: a review of its discovery, chemical properties, pre-clinical development and clinical trials. Cancer Treat Rev. 1997;23(1):35–61.

    Article  PubMed  CAS  Google Scholar 

  61. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.

    Article  PubMed  CAS  Google Scholar 

  62. Christodoulou C, Bafaloukos D, Kosmidis P, et al. Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases. Ann Oncol. 2001;12(2):249–54.

    Article  PubMed  CAS  Google Scholar 

  63. Dziadziuszko R, Ardizzoni A, Postmus PE, et al. Temozolomide in patients with advanced non-small cell lung cancer with and without brain metastases: a phase II study of the EORTC Lung Cancer Group (08965). Eur J Cancer. 2003;39(9):1271–6.

    Article  PubMed  CAS  Google Scholar 

  64. Giorgio CG, Giuffrida D, Pappalardo A, et al. Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study. Lung Cancer. 2005;50(2):247–54.

    Article  PubMed  Google Scholar 

  65. Siena S, Crino L, Danova M, et al. Dose-dense temozolomide regimen for the treatment of brain metastases from melanoma, breast cancer, or lung cancer not amenable to surgery or radiosurgery: a multicenter phase II study. Ann Oncol. 2010;21(3):655–61.

    Article  PubMed  CAS  Google Scholar 

  66. Rivera E, Meyers C, Groves M, et al. Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma. Cancer. 2006;107(6):1348–54.

    Article  PubMed  CAS  Google Scholar 

  67. Murphy C, Nulsen B, Rump M, et al. Phase II trial of patupilone in patients (pts) with breast cancer brain metastases (BCBM) progressing or recurring after whole brain radiotherapy (WBXRT) (abstract no. 234). ASCO breast cancer symposium, 8–10 Oct 2009, San Francisco (CA).

  68. Lassman AB, Abrey LE, Shah GD, et al. Systemic high-dose intravenous methotrexate for central nervous system metastases. J Neurooncol. 2006;78(3):255–60.

    Article  PubMed  CAS  Google Scholar 

  69. Antonadou D, Paraskevaidis M, Sarris G, et al. Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Oncol. 2002;20(17):3644–50.

    Article  PubMed  CAS  Google Scholar 

  70. Verger E, Gil M, Yaya R, et al. Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial. Int J Radiat Oncol Biol Phys. 2005;61(1):185–91.

    Article  PubMed  CAS  Google Scholar 

  71. Bartsch R, De Vries C, Pluschnig U, et al. Predicting for activity of second-line trastuzumab-based therapy in HER2-positive advanced breast cancer. BMC Cancer. 2009;9:367.

    Article  PubMed  CAS  Google Scholar 

  72. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.

    Article  PubMed  CAS  Google Scholar 

  73. Pestalozzi BC, Brignoli S. Trastuzumab in CSF. J Clin Oncol. 2000;18(11):2349–51.

    PubMed  CAS  Google Scholar 

  74. Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin Cancer Res. 2007;13(6):1648–55.

    Article  PubMed  CAS  Google Scholar 

  75. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355(26):2733–43.

    Article  PubMed  CAS  Google Scholar 

  76. Tykerb® (lapatinib) tablets: full prescribing information (online). http://us.gsk.com/products/assets/us_tykerb.pdf. Accessed 22 Apr 2012.

  77. Lin NU, Dieras V, Paul D, et al. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res. 2009;15(4):1452–9.

    Article  PubMed  CAS  Google Scholar 

  78. Lin NU, Eierman W, Greil R, et al. Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases. J Neurooncol. 2011;105(3):613–20.

    Article  PubMed  CAS  Google Scholar 

  79. Taskar KS, Rudraraju V, Mittapalli RK, et al. Lapatinib distribution in HER2 overexpressing experimental brain metastases of breast cancer. Pharm Res. 2012;29(3):770–81.

    Article  PubMed  CAS  Google Scholar 

  80. Blackwell KL, Burstein HJ, Storniolo AM, et al. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010;28(7):1124–30.

    Article  PubMed  CAS  Google Scholar 

  81. Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012;379(9816):633–40.

    Article  PubMed  CAS  Google Scholar 

  82. Gianni L, Llado A, Bianchi G, et al. Open-label, phase II, multicenter, randomized study of the efficacy and safety of two dose levels of pertuzumab, a human epidermal growth factor receptor 2 dimerization inhibitor, in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2010;28(7):1131–7.

    Article  PubMed  CAS  Google Scholar 

  83. Baselga J, Cortes J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109–19.

    Article  PubMed  CAS  Google Scholar 

  84. Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987;235(4787):442–7.

    Article  PubMed  CAS  Google Scholar 

  85. Friedman HS, Prados MD, Wen PY, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27(28):4733–40.

    Article  PubMed  CAS  Google Scholar 

  86. Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 2001;19(3):843–50.

    PubMed  CAS  Google Scholar 

  87. Besse B, Lasserre SF, Compton P, et al. Bevacizumab safety in patients with central nervous system metastases. Clin Cancer Res. 2010;16(1):269–78.

    Article  PubMed  CAS  Google Scholar 

  88. Socinski MA, Langer CJ, Huang JE, et al. Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases. J Clin Oncol. 2009;27(31):5255–61.

    Article  PubMed  CAS  Google Scholar 

  89. Labidi SI, Bachelot T, Ray-Coquard I, et al. Bevacizumab and paclitaxel for breast cancer patients with central nervous system metastases: a case series. Clin Breast Cancer. 2009;9(2):118–21.

    Article  PubMed  CAS  Google Scholar 

  90. Lu Y, Chen W, Lin C, et al. Bevacizumab, etoposide, and cisplatin (BEEP) in brain metastases of breast cancer progressing from radiotherapy: results of the first stage of a multicenter phase II study (abstract). J Clin Oncol. 2012;30(Suppl.);1079.

  91. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357(26):2666–76.

    Article  PubMed  CAS  Google Scholar 

  92. De Braganca KC, Janjigian YY, Azzoli CG, et al. Efficacy and safety of bevacizumab in active brain metastases from non-small cell lung cancer. J Neurooncol. 2010;100(3):443–7.

    Article  PubMed  CAS  Google Scholar 

  93. Mathews MS, Linskey ME, Hasso AN, et al. The effect of bevacizumab (Avastin) on neuroimaging of brain metastases. Surg Neurol. 2008;70(6):649–52 (discussion 653).

    Google Scholar 

  94. Leenders WP, Kusters B, Verrijp K, et al. Antiangiogenic therapy of cerebral melanoma metastases results in sustained tumor progression via vessel co-option. Clin Cancer Res. 2004;10(18 Pt 1):6222–30.

    Article  PubMed  CAS  Google Scholar 

  95. Kienast Y, von Baumgarten L, Fuhrmann M, et al. Real-time imaging reveals the single steps of brain metastasis formation. Nat Med. 2010;16(1):116–22.

    Article  PubMed  CAS  Google Scholar 

  96. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–717.

    Google Scholar 

  97. Lien EA, Wester K, Lonning PE, et al. Distribution of tamoxifen and metabolites into brain tissue and brain metastases in breast cancer patients. Br J Cancer. 1991;63(4):641–5.

    Article  PubMed  CAS  Google Scholar 

  98. Chen J, Balmaceda C, Bruce JN, et al. Tamoxifen paradoxically decreases paclitaxel deposition into cerebrospinal fluid of brain tumor patients. J Neurooncol. 2006;76(1):85–92.

    Article  PubMed  CAS  Google Scholar 

  99. Fine RL, Chen J, Balmaceda C, et al. Randomized study of paclitaxel and tamoxifen deposition into human brain tumors: implications for the treatment of metastatic brain tumors. Clin Cancer Res. 2006;12(19):5770–6.

    Article  PubMed  CAS  Google Scholar 

  100. Iusuf D, Teunissen SF, Wagenaar E, et al. P-glycoprotein (ABCB1) transports the primary active tamoxifen metabolites endoxifen and 4-hydroxytamoxifen and restricts their brain penetration. J Pharmacol Exp Ther. 2011;337(3):710–7.

    Article  PubMed  CAS  Google Scholar 

  101. Lin N, Ramakrishna N, Younger W, et al. Phase I study of lapatinib (L) in combination with whole-brain radiation therapy (WBRT) in patients (pts) with brain metastases from HER2-positive breast cancer (abstract). J Clin Oncol. 2010;28(Suppl. 15):1154.

    Google Scholar 

  102. Chargari C, Idrissi HR, Pierga JY, et al. Preliminary results of whole brain radiotherapy with concurrent trastuzumab for treatment of brain metastases in breast cancer patients. Int J Radiat Oncol Biol Phys. 2011;81(3):631–6.

    Article  PubMed  Google Scholar 

  103. Kocher M, Soffietti R, Abacioglu U, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952–26001 study. J Clin Oncol. 2011;29(2):134–41.

    Article  PubMed  Google Scholar 

  104. Cameron D, Casey M, Press M, et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008;112(3):533–43.

    Article  PubMed  CAS  Google Scholar 

  105. Duchnowska R, Biernat W, Szostakiewicz B, et al. Correlation between quantitative HER-2 protein expression and risk for brain metastases in HER-2+ advanced breast cancer patients receiving trastuzumab-containing therapy. Oncologist. 2012;17(1):26–35.

    Article  PubMed  CAS  Google Scholar 

  106. Duchnowska R, Jassem J, Goswami C, et al. 13-gene signature to predict rapid development of brain metastases in patients with HER2-positive advanced breast cancer (abstract). J Clin Oncol. 2012;30(Suppl. 15):505.

    Google Scholar 

  107. Gril B, Palmieri D, Qian Y, et al. Pazopanib reveals a role for tumor cell B-Raf in the prevention of HER2+ breast cancer brain metastasis. Clin Cancer Res. 2011;17(1):142–53.

    Article  PubMed  CAS  Google Scholar 

  108. de Azevedo CR, Cruz MR, Chinen LT, et al. Meningeal carcinomatosis in breast cancer: prognostic factors and outcome. J Neurooncol. 2011;104(2):565–72.

    Article  PubMed  Google Scholar 

  109. Gauthier H, Guilhaume MN, Bidard FC, et al. Survival of breast cancer patients with meningeal carcinomatosis. Ann Oncol. 2010;21(11):2183–7.

    Article  PubMed  CAS  Google Scholar 

  110. Rakha EA, El-Sayed ME, Green AR, et al. Prognostic markers in triple-negative breast cancer. Cancer. 2007;109(1):25–32.

    Article  PubMed  CAS  Google Scholar 

  111. Gani C, Muller AC, Eckert F, et al. Outcome after whole brain radiotherapy alone in intracranial leptomeningeal carcinomatosis from solid tumors. Strahlenther Onkol. 2012;188(2):148–53.

    Article  PubMed  CAS  Google Scholar 

  112. Chamberlain MC. Neoplastic meningitis. Oncologist. 2008;13(9):967–77.

    Article  PubMed  Google Scholar 

  113. Chamberlain MC, Kormanik PR. Carcinomatous meningitis secondary to breast cancer: predictors of response to combined modality therapy. J Neurooncol. 1997;35(1):55–64.

    Article  PubMed  CAS  Google Scholar 

  114. Jaeckle KA, Phuphanich S, Bent MJ, et al. Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine. Br J Cancer. 2001;84(2):157–63.

    Article  PubMed  CAS  Google Scholar 

  115. Kim S, Chatelut E, Kim JC, et al. Extended CSF cytarabine exposure following intrathecal administration of DTC 101. J Clin Oncol. 1993;11(11):2186–93.

    PubMed  CAS  Google Scholar 

  116. Grossman SA, Finkelstein DM, Ruckdeschel JC, et al. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis: Eastern Cooperative Oncology Group. J Clin Oncol. 1993;11(3):561–9.

    PubMed  CAS  Google Scholar 

  117. Glantz MJ, Jaeckle KA, Chamberlain MC, et al. A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res. 1999;5(11):3394–402.

    PubMed  CAS  Google Scholar 

  118. Rogers LR, Remer SE, Tejwani S. Durable response of breast cancer leptomeningeal metastasis to capecitabine monotherapy. Neuro Oncol. 2004;6(1):63–4.

    Article  PubMed  Google Scholar 

  119. Boogerd W, Dorresteijn LD, van Der Sande JJ, et al. Response of leptomeningeal metastases from breast cancer to hormonal therapy. Neurology. 2000;55(1):117–9.

    Article  PubMed  CAS  Google Scholar 

  120. Boogerd W, van den Bent MJ, Koehler PJ, et al. The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study. Eur J Cancer. 2004;40(18):2726–33.

    Article  PubMed  CAS  Google Scholar 

  121. Bokstein F, Lossos A, Siegal T. Leptomeningeal metastases from solid tumors: a comparison of two prospective series treated with and without intra-cerebrospinal fluid chemotherapy. Cancer. 1998;82(9):1756–63.

    Article  PubMed  CAS  Google Scholar 

  122. Oliveira M, Braga S, Passos-Coelho JL, et al. Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab. Breast Cancer Res Treat. 2011;127(3):841–4.

    Article  PubMed  CAS  Google Scholar 

  123. Mego M, Sycova-Mila Z, Obertova J, et al. Intrathecal administration of trastuzumab with cytarabine and methotrexate in breast cancer patients with leptomeningeal carcinomatosis. Breast. 2011;20(5):478–80.

    Article  PubMed  Google Scholar 

  124. Laufman LR, Forsthoefel KF. Use of intrathecal trastuzumab in a patient with carcinomatous meningitis (letter). Clin Breast Cancer. 2001;2(3):235.

    Article  PubMed  CAS  Google Scholar 

  125. Stemmler HJ, Mengele K, Schmitt M, et al. Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report. Anticancer Drugs. 2008;19(8):832–6.

    Article  PubMed  CAS  Google Scholar 

  126. Platini C, Long J, Walter S. Meningeal carcinomatosis from breast cancer treated with intrathecal trastuzumab. Lancet Oncol. 2006;7(9):778–80.

    Article  PubMed  Google Scholar 

  127. Colozza M, Minenza E, Gori S, et al. Extended survival of a HER-2-positive metastatic breast cancer patient with brain metastases also treated with intrathecal trastuzumab. Cancer Chemother Pharmacol. 2009;63(6):1157–9.

    Article  PubMed  Google Scholar 

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Acknowledgements

No sources of funding were received to prepare this article. Rupert Bartsch has received lecture honoraria from Glaxo-Smith-Kline and Hoffmann-La Roche and research support from Hoffmann-La Roche. All other authors declare that they have no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Medicine I, Clinical Division of Oncology, Comprehensive Cancer Centre, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria

    Rupert Bartsch & Matthias Preusser

  2. Comprehensive Cancer Centre, Medical University of Vienna, Vienna, Austria

    Rupert Bartsch, Anna S. Berghoff & Matthias Preusser

  3. Institute of Neurology, Medical University of Vienna, Vienna, Austria

    Anna S. Berghoff

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  1. Rupert Bartsch
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  2. Anna S. Berghoff
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  3. Matthias Preusser
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Correspondence to Matthias Preusser.

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Bartsch, R., Berghoff, A.S. & Preusser, M. Optimal Management of Brain Metastases from Breast Cancer. CNS Drugs 27, 121–134 (2013). https://doi.org/10.1007/s40263-012-0024-z

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