Chemotherapy and biological treatment options in breast cancer patients with brain metastasis: An update

Expert Opinion on Pharmacotherapy

Volumn 15, Issue 12, 2014, Pages 1643-1658

  Arslan, Cagatay ^a   Dizdar, Omer ^b   Altundag, Kadri ^c  

^a MEDICAL PARK HOSPITAL   (Turkey)

^b Baskent Universitesi Ankara Hastanesi   (Turkey)

^c HACETTEPE UNIVERSITY   (Turkey)

Author keywords

Biological agents; Brain metastasis; Breast cancer; Chemotherapy

Indexed keywords

ALPHA [AMINO(4 AMINOPHENYLTHIO)METHYLENE] 2 (TRIFLUOROMETHYL)PHENYLACETONITRILE; ANTINEOPLASTIC AGENT; BENDAMUSTINE; BEVACIZUMAB; BLEOMYCIN; CAPECITABINE; CISPLATIN DERIVATIVE; CORTICOSTEROID DERIVATIVE; CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; ETOPOSIDE; FLUOROURACIL; GEMCITABINE; IDARUBICIN; LAPATINIB; METHOTREXATE; NAVELBINE; PACLITAXEL; PAZOPANIB; SAGOPILONE; SARACATINIB; TEMOZOLOMIDE; TEMSIROLIMUS; TOPOTECAN; TRASTUZUMAB; UNINDEXED DRUG; VINBLASTINE; VINCRISTINE; VORINOSTAT;

BRAIN METASTASIS; BREAST CANCER; BREAST METASTASIS; CANCER CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER PATIENT; CANCER PREVENTION; CANCER RADIOTHERAPY; CANCER SURGERY; CORTICOSTEROID THERAPY; DRUG MEGADOSE; HUMAN; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STEREOTACTIC BODY RADIATION THERAPY; SYSTEMIC THERAPY;

BIOLOGICAL AGENTS; BRAIN METASTASIS; BREAST CANCER; CHEMOTHERAPY;

ANIMALS; ANTINEOPLASTIC AGENTS; BRAIN; BRAIN NEOPLASMS; BREAST; BREAST NEOPLASMS; DEOXYCYTIDINE; FEMALE; FLUOROURACIL; HUMANS; QUINAZOLINES;

EID: 84904694824     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2014.929664     Document Type: Review

References (126)

1. Walker AE, Robins M, Weinfeld FD. Epidemiology of brain tumors: The national survey of intracranial neoplasms. Neurology 1985;35:219-26
2. Percy AK, Elveback LR, Okazaki H, Kurland LT. Neoplasms of the central nervous system. Epidemiologic considerations. Neurology 1972;22:40-8
3. Lin NU, Bellon JR, Winer EP. CNS metastases in breast cancer. J Clin Oncol 2004;22:3608-17
4. Tham YL, Sexton K, Kramer R, et al. Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 2006;107:696-704
5. Nussbaum ES, Djalilian HR, Cho KH, Hall WA. Brain metastases. Histology, multiplicity, surgery, and survival. Cancer 1996;78:1781-8
6. Tsukada Y, Fouad A, Pickren JW, Lane WW. Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer 1983;52:2349-54
7. 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;17:4834-43
8. Issa CM, Semrau R, Kath R, Hoffken K. Isolated brain metastases as the sole manifestation of a late relapse in breast cancer. J Cancer Res Clin Oncol 2002;128:61-3
9. Boogerd W, Vos VW, Hart AA, Baris G. Brain metastases in breast cancer; natural history, prognostic factors and outcome. J Neurooncol 1993;15:165-74
10. 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;37:745-51
11. 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;16:345-9
12. Hicks DG, Short SM, Prescott NL, 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. Am J Surg Pathol 2006;30:1097-104
13. 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;14:1072-7
14. Gonzalez-Angulo AM, Cristofanilli M, Strom EA, et al. Central nervous system metastases in patients with high-risk breast carcinoma after multimodality treatment. Cancer 2004;101:1760-76
15. Ryberg M, Nielsen D, Osterlind K, et al. Predictors of central nervous system metastasis in patients with metastatic breast cancer. A competing risk analysis of 579 patients treated with epirubicinbased chemotherapy. Breast Cancer Res Treat 2005;91:217-25
16. 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;24:5658-63
17. Clayton AJ, Danson S, Jolly S, et al. Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 2004;91:639-43
18. Stemmler HJ, Kahlert S, Siekiera W, et al. Characteristics of patients with brain metastases receiving trastuzumab for HER2 overexpressing metastatic breast cancer. Breast 2006;15:219-25
19. Bendell JC, Domchek SM, Burstein HJ, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 2003;97:2972-7
20. 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;45:196-201
21. Shmueli E, Wigler N, Inbar M. Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment. Eur J Cancer 2004;40:379-82
22. Altundag K, Bondy ML, Mirza NQ, et al. Clinicopathologic characteristics and prognostic factors in 420 metastatic breast cancer patients with central nervous system metastasis. Cancer 2007;110:2640-7
23. Harputluoglu H, Dizdar O, Aksoy S, et al. Characteristics of breast cancer patients with central nervous system metastases: A single-center experience. J Natl Med Assoc 2008;100:521-6
24. Lagerwaard FJ, Levendag PC, Nowak PJ, et al. Identification of prognostic factors in patients with brain metastases: A review of 1292 patients. Int J Radiat Oncol Biol Phys 1999;43:795-803
25. Kim HJ, Im SA, Keam B, et al. Clinical outcome of central nervous system metastases from breast cancer: Differences in survival depending on systemic treatment. J Neurooncol 2012;106:303-13
26. Lee SS, Ahn JH, Kim MK, et al. Brain metastases in breast cancer: Prognostic factors and management. Breast Cancer Res Treat 2008;111:523-30
27. Boogerd W, Dalesio O, Bais EM, Van der Sande JJ. Response of brain metastases from breast cancer to systemic chemotherapy. Cancer 1992;69:972-80
28. Nieder C, Berberich W, Schnabel K. Tumor-related prognostic factors for remission of brain metastases after radiotherapy. Int J Radiat Oncol Biol Phys 1997;39:25-30
29. Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322:494-500
30. Shiau CY, Sneed PK, Shu HK, et al. Radiosurgery for brain metastases: Relationship of dose and pattern of enhancement to local control. Int J Radiat Oncol Biol Phys 1997;37:375-83
31. Meng FL, Zhou QH, Zhang LL, et al. Antineoplastic therapy combined with whole brain radiation compared with whole brain radiation alone for brain metastases: A systematic review and meta-Analysis. Eur Rev Med Pharmacol Sci 2013;17:777-87
32. Sperduto PW, Wang M, Robins HI, et al. A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases: Radiation Therapy Oncology Group 0320. Int J Radiat Oncol Biol Phys 2013;85:1312-18
33. Pesce GA, Klingbiel D, Ribi K, et al. Outcome, quality of life and cognitive function of patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy combined with gefitinib or temozolomide. A randomised phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 70/03). Eur J Cancer 2012;48:377-84
34. Langley RR, Fidler IJ. The biology of brain metastasis. Clin Chem 2013;59:180-9
35. Palmieri D, Smith QR, Lockman PR, et al. Brain metastases of breast cancer. Breast Dis 2006;26:139-47
36. Wu YJ, Muldoon LL, Gahramanov S, et al. Targeting alphaV-integrins decreased metastasis and increased survival in a nude rat breast cancer brain metastasis model. J Neurooncol 2012;110:27-36
37. Vogetseder A, Thies S, Ingold B, et al. alphav-Integrin isoform expression in primary human tumors and brain metastases. Int J Cancer 2013;133:2362-71
38. Malin D, Strekalova E, Petrovic V, et al. alphaB-crystallin: A novel regulator of breast cancer metastasis to the brain. Clin Cancer Res 2014;20:56-67
39. Kienast Y, von Baumgarten L, Fuhrmann M, et al. Real-Time imaging reveals the single steps of brain metastasis formation. Nat Med 2010;16:116-22
40. Weil RJ, Palmieri DC, Bronder JL, et al. Breast cancer metastasis to the central nervous system. Am J Pathol 2005;167:913-20
41. Kim SJ, Kim JS, Park ES, et al. Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy. Neoplasia 2011;13:286-98
42. Bos PD, Zhang XH, Nadal C, et al. Genes that mediate breast cancer metastasis to the brain. Nature 2009;459:1005-9
43. Palmieri D, Fitzgerald D, Shreeve SM, et al. Analyses of resected human brain metastases of breast cancer reveal the association between up-regulation of hexokinase 2 and poor prognosis. Mol Cancer Res 2009;7:1438-45
44. Sanz-Pamplona R, Aragues R, Driouch K, et al. Expression of endoplasmic reticulum stress proteins is a candidate marker of brain metastasis in both ErbB-2+ and ErbB-2-primary breast tumors. Am J Pathol 2011;179:564-79
45. Xenidis N, Perraki M, Kafousi M, et al. Predictive and prognostic value of peripheral blood cytokeratin-19 mRNApositive cells detected by real-Time polymerase chain reaction in nodenegative breast cancer patients. J Clin Oncol 2006;24:3756-62
46. Souglakos J, Vamvakas L, Apostolaki S, et al. 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. Breast Cancer Res 2006;8:R36
47. Arslan C, Dizdar O, Altundag K. Systemic treatment in breast-cancer patients with brain metastasis. Expert Opin Pharmacother 2010;11:1089-100
48. Muldoon LL, Soussain C, Jahnke K, et al. Chemotherapy delivery issues in central nervous system malignancy: A reality check. J Clin Oncol 2007;25:2295-305
49. Siegal T. Which drug or drug delivery system can change clinical practice for brain tumor therapy?. Neuro Oncol 2013;15:656-69
50. Wang ML, Yung WK, Royce ME, et al. Capecitabine for 5-fluorouracil- resistant brain metastases from breast cancer. Am J Clin Oncol 2001;24:421-4
51. Zulkowski K, Kath R, Semrau R, et al. Regression of brain metastases from breast carcinoma after chemotherapy with bendamustine. J Cancer Res Clin Oncol 2002;128:111-13
52. Kurt M, Aksoy S, Hayran M, Guler N. A retrospective review of breast cancer patients with central nervous system metastasis treated with capecitabine [abstract no: 1098]. ASCO Annual Meeting; 2007
53. Boogerd W, Tjahja IS, Van de Sandt MM, Beijnen JH. Penetration of idarubicin into malignant brain tumor tissue. J Neurooncol 1999;44:65-9
54. Freilich RJ, Seidman AD, DeAngelis LM. Central nervous system progression of metastatic breast cancer in patients treated with paclitaxel. Cancer 1995;76:232-6
55. Crivellari D, Pagani O, Veronesi A, et al. High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel. Ann Oncol 2001;12:353-6
56. Schwonzen M, Kurbacher CM, Mallmann P. Liposomal doxorubicin and weekly paclitaxel in the treatment of metastatic breast cancer. Anticancer Drugs 2000;11:681-5
57. Wilson WH, Berg SL, Bryant G, et al. Paclitaxel in doxorubicin-refractory or mitoxantrone-refractory breast cancer: A phase I/II trial of 96-hour infusion. J Clin Oncol 1994;12:1621-9
58. Pestalozzi BC, Francis P, Quinaux E, et al. Is risk of central nervous system (CNS) relapse related to adjuvant taxane treatment in node-positive breast cancer?. Results of the CNS substudy in the intergroup Phase III BIG 02-98 Trial. Ann Oncol 2008;19:1837-41
59. 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;9:118-21
60. Baker SD, Heideman RL, Crom WR, et al. Cerebrospinal fluid pharmacokinetics and penetration of continuous infusion topotecan in children with central nervous system tumors. Cancer Chemother Pharmacol 1996;37:195-202
61. Zamboni WC, Luftner DI, Egorin MJ, et al. The effect of increasing topotecan infusion from 30 minutes to 4 hours on the duration of exposure in cerebrospinal fluid. Ann Oncol 2001;12:119-22
62. Oberhoff C, Kieback DG, Wurstlein R, et al. Topotecan chemotherapy in patients with breast cancer and brain metastases: Results of a pilot study. Onkologie 2001;24:256-60
63. Gruschow K, Klautke G, Fietkau R. Phase I/II clinical trial of concurrent radiochemotherapy in combination with topotecan for the treatment of brain metastases. Eur J Cancer 2002;38:367-74
64. Kocher M, Eich HT, Semrau R, et al. Phase I/II trial of simultaneous wholebrain irradiation and dose-escalating topotecan for brain metastases. Strahlenther Onkol 2005;181:20-5
65. Hedde JP, Neuhaus T, Schuller H, et al. A phase I/II trial of topotecan and radiation therapy for brain metastases in patients with solid tumors. Int J Radiat Oncol Biol Phys 2007;68:839-44
66. Stewart DJ, Mikhael NZ, Nair RC, et al. Platinum concentrations in human autopsy tumor samples. Am J Clin Oncol 1988;11:152-8
67. Cocconi G, Lottici R, Bisagni G, et al. Combination therapy with platinum and etoposide of brain metastases from breast carcinoma. Cancer Invest 1990;8:327-34
68. Franciosi V, Cocconi G, Michiara M, et al. Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma: A prospective study. Cancer 1999;85:1599-605
69. Ekenel M, Hormigo AM, Peak S, et al. Capecitabine therapy of central nervous system metastases from breast cancer. J Neurooncol 2007;85:223-7
70. Naskhletashvili DR, Gorbounova VA, Bychkov MB, et al Capecitabine monotherapy for patients with brain metastases from advanced breast cancer [abstract no: 1102]. ASCO Annual Meeting; 2009
71. 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;107:1348-54
72. Stupp R, Gander M, Leyvraz S, Newlands E. Current and future developments in the use of temozolomide for the treatment of brain tumours. Lancet Oncol 2001;2:552-60
73. Abrey LE, Olson JD, Raizer JJ, et al. A phase II trial of temozolomide for patients with recurrent or progressive brain metastases. J Neurooncol 2001;53:259-65
74. Christodoulou C, Bafaloukos D, Kosmidis P, et al. Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases. Ann Oncol 2001;12:249-54
75. Preuss I, Eberhagen I, Haas S, et al. O6-methylguanine-DNA methyltransferase activity in breast and brain tumors. Int J Cancer 1995;61:321-6
76. Tosoni A, Franceschi E, Ermani M, et al. Temozolomide three weeks on and one week off as first line therapy for patients with recurrent or progressive low grade gliomas. J Neurooncol 2008;89:179-85
77. Brandes AA, Tosoni A, Cavallo G, et al Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: Phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO). Br J Cancer 2006;95:1155-60
78. Palmieri D, Duchnowska R, Woditschka S, et al. Profound prevention of experimental brain metastases of breast cancer by temozolomide in an MGMTdependent manner. Clin Cancer Res 2014. [Epub ahead of print]
79. Trudeau ME, Crump M, Charpentier D, et al. Temozolomide in metastatic breast cancer (MBC): A phase II trial of the National Cancer Institute of Canada-Clinical Trials Group (NCIC-CTG). Ann Oncol 2006;17:952-6
80. Friedman HS. Phase II trial of temozolomide for patients with progressive brain metastases. ASCO Annual Meeting (Central Nervous System Session, Poster Discussion); 2003
81. Addeo R, De Rosa C, Faiola V, et al. Phase 2 trial of temozolomide using protracted low-dose and whole-brain radiotherapy for nonsmall cell lung cancer and breast cancer patients with brain metastases. Cancer 2008;113:2524-31
82. Kouvaris JR, Miliadou A, Kouloulias VE, et al. Phase II study of temozolomide and concomitant whole-brain radiotherapy in patients with brain metastases from solid tumors. Onkologie 2007;30:361-6
83. Kirova YM, Hajage D, Gerber S, et al. Whole-brain radiation therapy plus concomitant temozolomide for the treatment of brain metastases from breast cancer: A randomized prospective multicenter phase II study [abstract: P4-17-02]. San Antonio Breast Cancer Symposium; 2011
84. 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;20:3644-50
85. 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;61:185-91
86. Christodoulou C, Bafaloukos D, Linardou H, et al. Temozolomide (TMZ) combined with cisplatin (CDDP) in patients with brain metastases from solid tumors: A Hellenic Cooperative Oncology Group (HeCOG) Phase II study. J Neurooncol 2005;71:61-5
87. Melisko ME, Anderson M, Scott J, et al Phase II study of irinotecan and temozolomide in breast cancer patients with brain metastases or leptomeningeal disease that has progressed after stereotactic radiosurgery or whole brain radiation [abstract no:237]. ASCO Breast cancer Symposium; 2009
88. Caraglia M, Addeo R, Costanzo R, et al Pegylated liposomal doxorubicin plus temozolomide in the salvage treatment of brain metastases: The update [abstract no:1576]. ASCO Annual Meeting; 2004
89. Iwamoto FM, Omuro AM, Raizer JJ, et al. A phase II trial of vinorelbine and intensive temozolomide for patients with recurrent or progressive brain metastases. J Neurooncol 2008;87:85-90
90. Omuro AM, Raizer JJ, Demopoulos A, et al. Vinorelbine combined with a protracted course of temozolomide for recurrent brain metastases: A phase I trial. J Neurooncol 2006;78:277-80
91. Rosner D, Nemoto T, Lane WW. Chemotherapy induces regression of brain metastases in breast carcinoma. Cancer 1986;58:832-9
92. Donadio M, Ardine M, Berruti A, et al. Gemcitabine and vinorelbine as secondline treatment in patients with metastatic breast cancer: A phase II study. Cancer Chemother Pharmacol 2003;52:147-52
93. Murphy C, Nulsen B, Rump M, et al Phase II trial of patupilone in patients with breast cancer metastases progressing or recurring after whole brain radiotherapy [abstract no:234]. ASCO Breast Cancer Symposium; 2009
94. Conlin AK, D'andrea G, Hudis CA, et al Phase II trial of patupilone in patients with breast cancer brain metastases progressing or recurring after whole brain radiotherapy [abstract no:1086]. ASCO Annual Meeting; 2008
95. Freedman RA, Bullit E, Sun L, et al. A phase II study of sagopilone (ZK 219477; ZK-EPO) in patients with breast cancer and brain metastases. Clin Breast Cancer 2013;11:376-83
96. Lin NU, Schwartzberg LS, Kesari SA, et al. Phase 2, multi-center, open label study evaluating the efficacy and safety of GRN1005 alone or in combination with trastuzumab in patients with brain metastases from breast cancer [abstract: P3-12-04]. San Antonio Breast Cancer Symposium; 2012
97. Glantz MJ, Cole BF, Recht L, et al. High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: Is intrathecal chemotherapy necessary?. J Clin Oncol 1998;16:1561-7
98. Lassman AB, Abrey LE, Shah GD, et al. Systemic high-dose intravenous methotrexate for central nervous system metastases. J Neurooncol 2006;78:255-60
99. Leyland-Jones B. Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases. J Clin Oncol 2009;27:5278-86
100. 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;18:23-8
101. Park YH, Park MJ, Ji SH, et al. Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients. Br J Cancer 2009;100:894-900
102. Kodack DP, Chung E, Yamashita H, et al. Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-Amplified breast cancer brain metastases. Proc Natl Acad Sci USA 2012;109:E3119-27
103. Platini C, Long J, Walter S. Meningeal carcinomatosis from breast cancer treated with intrathecal trastuzumab. Lancet Oncol 2006;7:778-80
104. Mir O, Ropert S, Alexandre J, et al. High-dose intrathecal trastuzumab for leptomeningeal metastases secondary to HER-2 overexpressing breast cancer. Ann Oncol 2008;19:1978-80
105. Taskar KS, Rudraraju V, Mittapalli RK, et al. Lapatinib distribution in HER2 overexpressing experimental brain metastases of breast cancer. Pharm Res 2012;29:770-81
106. 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;112:533-43
107. Kaplan MA, Isikdogan A, Koca D, et al. Clinical outcomes in patients who received lapatinib plus capecitabine combination therapy for HER2-positive breast cancer with brain metastasis and a comparison of survival with those who received trastuzumab-based therapy: A study by the Anatolian Society of Medical Oncology. Breast Cancer 2013;published online 19 January 2013; doi:10.1007/s12282-013-0441-y
108. Gril B, Palmieri D, Bronder JL, et al. Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain. J Natl Cancer Inst 2008;100:1092-103
109. Lin NU, Carey LA, Liu MC, et al. Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 2008;26:1993-9
110. 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;15:1452-9
111. Bachelot T, Romieu G, Campone M, et al. Lapatinib plus capecitabine in patients with previously untreated brain metastases from HER2-positive metastatic breast cancer (LANDSCAPE): A single-group phase 2 study. Lancet Oncol 2013;14:64-71
112. Lin NU, Eiermann 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;105:613-20
113. Lin NU, Freedman RA, Ramakrishna N. A phase I study of lapatinib with whole brain radiotherapy in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer brain metastases. Breast Cancer Res Treat 2013;142:405-14
114. 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;27:5255-61
115. Lu Y-S, Chen W-W, Lin C-H, 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 no: 1079]. ASCO Annual Meeting; 2012
116. Lu Y-S, Chen W-W, Lin C-H, et al. Bevacizumab, etoposide, and cisplatin (BEEP) is highly effective in brain metastases of HER2 positive breast cancer progressing from whole brain radiotherapy-subgroup analysis of a multi-center phase II study [abstract: P2-16-02]. San Antonio Breast Cancer Symposium; 2013
117. Doothe B, Young R, Yamada Y, et al. Bevacizumab as a treatment for radiation necrosis of brain metastases post stereotactic radiosurgery. Neuro-oncol 2013;15:1257-63
118. Palmieri D, Lockman PR, Thomas FC, et al. Vorinostat inhibits brain metastatic colonization in a model of triple-negative breast cancer and induces DNA double-strand breaks. Clin Cancer Res 2009;15:6148-57
119. Baschnagel A, Russo A, Burgan WE, et al. Vorinostat enhances the radiosensitivity of a breast cancer brain metastatic cell line grown in vitro and as intracranial xenografts. Mol Cancer Ther 2009;8:1589-95
120. 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;17:142-53
121. Gril B, Palmieri D, Qian Y, et al. Pazopanib inhibits the activation of PDGFRb-expressing astrocytes in the brain metastatic microenvironment of breast cancer cells. Am J Pathol 2013;182:2368-79
122. Zhang S, Huang WC, Zhang L, et al. Src family kinases as novel therapeutic targets to treat breast cancer brain metastases. Cancer Res 2013;73:5764-74
123. Nakayama A, Takagi S, Yusa T, et al. Antitumor activity of TAK-285, an investigational, non-Pgp substrate HER2/EGFR kinase inhibitor, in cultured tumor cells, mouse and rat xenograft tumors, and in an HER2-positive brain metastasis model. J Cancer 2013;4:557-65
124. Zhao H, Cui K, Nie F, et al. The effect of mTOR inhibition alone or combined with MEK inhibitors on brain metastasis: An in vivo analysis in triple-negative breast cancer models. Breast Cancer Res Treat 2012;131:425-36
125. Huang F, Alrefae M, Langleben A, Roberge D. Prophylactic cranial irradiation in advanced breast cancer: A case for caution. Int J Radiat Oncol Biol Phys 2009;73:752-8
126. Qian Y, Hua E, Bisht K, et al. Inhibition of Polo-like kinase 1 prevents the growth of metastatic breast cancer cells in the brain. Clin Exp Metastasis 2011;28:899-908