Skip to main content

Advertisement

SpringerLink
Log in

Clinical Trials for Breast Cancer with Brain Metastases: Challenges and New Directions

  • Clinical Trials (MN Dickler, Section Editor)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

Brain metastases (BM) portend a poor prognosis among breast cancer patients. The management of breast cancer with brain metastases (BCBM) is multi-modal with local therapy consisting of radiation and/or surgery, albeit without durable responses, and systemic therapy playing an increasingly important role. Further clinical research is warranted to improve prognosis for BCBM. However, there are several challenges in studying this population. This review provides a general overview of BCBM and discusses unique aspects of conducting clinical trials and ongoing/future research in BCBM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Brufsky AM, Mayer M, Rugo HS, Kaufman PA, Tan-Chiu E, Tripathy D, 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. doi:10.1158/1078-0432.CCR-10-2962.

    Article  PubMed  CAS  Google Scholar 

  2. Nieder C, Spanne O, Mehta MP, Grosu AL, Geinitz H. Presentation, patterns of care, and survival in patients with brain metastases: what has changed in the last 20 years? Cancer. 2010. doi:10.1002/cncr.25707.

    Google Scholar 

  3. Graesslin O, Abdulkarim BS, Coutant C, Huguet F, Gabos Z, Hsu L, et al. Nomogram to predict subsequent brain metastasis in patients with metastatic breast cancer. J Clin Oncol. 2010;28:2032–7. doi:10.1200/JCO.2009.24.6314.

    Article  PubMed  Google Scholar 

  4. • Pivot XSV, Zurawski B, Allerton R, Fabi A, Ciruelos E, Parikh R, et al., editors. CEREBEL (EGF111438): an open label randomized phase III study comparing the incidence of CNS metastases in patients (pts) with HER2+ metastatic breast cancer (MBC), treated with lapatinib plus capecitabine (LC) vs trastuzumab plus capecitabine (TC). Vienna: The Annual Meeting of the European Society for Medical Oncology; 2012. This study showed a high prevalence of asymptomatic BM among HER2+ BC patients.

    Google Scholar 

  5. Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin Cancer Res. 2007;13:1648–55. doi:10.1158/1078-0432.CCR-06-2478.

    Article  PubMed  CAS  Google Scholar 

  6. Larsen PB, Kumler I, Nielsen DL. A systematic review of trastuzumab and lapatinib in the treatment of women with brain metastases from HER2-positive breast cancer. Cancer Treat Rev. 2013. doi:10.1016/j.ctrv.2013.01.006.

    PubMed  Google Scholar 

  7. Tsao MN, Rades D, Wirth A, Lo SS, Danielson BL, Gaspar LE, et al. Radiotherapeutic and surgical management for newly diagnosed brain metastasis/es: an American Society for Radiation Oncology evidence-based guideline (2012). In: Clinical Practice Guideline. The American Society for Radiation Oncology (ASTRO). https://http://www.astro.org/Clinical-Practice/Guidelines/Brain-metastases.aspx. 2012. Accessed June 18 2013.

  8. • Sperduto PW, Kased N, Roberge D, Chao ST, Shanley R, Luo X, et al. The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer. J Neurooncol. 2013. doi:10.1007/s11060-013-1083-9. This study provides prognostic information according to subtypes for patients with BCBM undergoing RT using "Sperduto" model.

    PubMed  Google Scholar 

  9. Niwinska A, Tacikowska M, Murawska M. The effect of early detection of occult brain metastases in HER2-positive breast cancer patients on survival and cause of death. Int J Radiat Oncol Biol Phys. 2010;77:1134–9. doi:10.1016/j.ijrobp.2009.06.030.

    Article  PubMed  Google Scholar 

  10. Lin NU. Brain metastases in HER2-positive breast cancer. Lancet Oncol. 2013;14:185–6. doi:10.1016/S1470-2045(13)70046-9.

    Article  PubMed  Google Scholar 

  11. Gaspar LE. VG, Gore EM, Bradley GM, Germano I, Ghafoori P, Henderson MA, et al. ACR appropriateness criteria: pre-irradiation evaluation and management of brain metastases. American College of Radiology. http://www.acr.org/~/media/ACR/Documents/AppCriteria/Oncology/PreIrradiationEvaluationBrainMetastases.pdf. 2011. Accessed June 18, 2013.

  12. Brogi E, Murphy CG, Johnson ML, Conlin AK, Hsu M, Patil S, et al. Breast carcinoma with brain metastases: clinical analysis and immunoprofile on tissue microarrays. Ann Oncol. 2011;22:2597–603. doi:10.1093/annonc/mdr022.

    Article  PubMed  CAS  Google Scholar 

  13. Oncology NCPGi. Central Nervous System Cancers. National Comprehensive Cancer Network. http://www.nccn.org. 2013. Accessed June 18, 2013.

  14. Yamamoto M, Kawabe T, Sato Y, Higuchi Y, Nariai T, Barfod BE, et al. A case-matched study of stereotactic radiosurgery for patients with multiple brain metastases: comparing treatment results for 1–4 vs >/= 5 tumors. J Neurosurg. 2013;118:1258–68. doi:10.3171/2013.3.JNS121900.

    Article  PubMed  Google Scholar 

  15. Tallet AV, Azria D, Barlesi F, Spano JP, Carpentier AF, Goncalves A, et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment. Radiat Oncol. 2012;7:77. doi:10.1186/1748-717X-7-77.

    Article  PubMed  Google Scholar 

  16. Minniti G, Clarke E, Lanzetta G, Osti MF, Trasimeni G, Bozzao A, et al. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol. 2011;6:48. doi:10.1186/1748-717X-6-48.

    Article  PubMed  Google Scholar 

  17. Yamamoto M, Kawabe T, Higuchi Y, Sato Y, Nariai T, Barfod BE, et al. Delayed complications in patients surviving at least 3 years after stereotactic radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 2013;85:53–60. doi:10.1016/j.ijrobp.2012.04.018.

    Article  PubMed  Google Scholar 

  18. • Morikawa A, Peereboom DM, Smith QR, Thorsheim H, Lockman PR, Simmons AJ, et al., editors. Clinical evidence for drug penetration of capecitabine and lapatinib uptake in resected brain metastases from women with metastatic breast cancer. Chicago: The Annual Meeting of American Society of Clinical Oncology; 2013. This is the first study to demonstrate detectable drug concentrations of capecitabine and lapatinib in the human BCBM tissue.

  19. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733–43. doi:10.1056/NEJMoa064320.

    Article  PubMed  CAS  Google Scholar 

  20. Lin NU, Dieras V, Paul D, Lossignol D, Christodoulou C, Stemmler HJ, 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. doi:10.1158/1078-0432.CCR-08-1080.

    Article  PubMed  CAS  Google Scholar 

  21. Lin NU, Carey LA, Liu MC, Younger J, Come SE, Ewend M, 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. doi:10.1200/JCO.2007.12.3588.

    Article  PubMed  CAS  Google Scholar 

  22. • Bachelot T, Romieu G, Campone M, Dieras V, Cropet C, Dalenc F, 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. doi:10.1016/S1470-2045(12)70432-1. This study evaluated capecitabine and lapatinib in WBRT-naïve BCBM patients and showed that the median time to WBRT was 8.3 months.

    Article  PubMed  CAS  Google Scholar 

  23. HKI-272 for HER2-positive breast cancer and brain metastases NCT01494662 [database on the Internet]. National Library of Medicine, Bethesda, MD, USA. 2000. Accessed: June 18, 2013.

  24. Preusser M, Winkler F, Collette L, Haller S, Marreaud S, Soffietti R, et al. Trial design on prophylaxis and treatment of brain metastases: lessons learned from the EORTC Brain Metastases Strategic Meeting 2012. Eur J Cancer. 2012;48:3439–47. doi:10.1016/j.ejca.2012.07.002.

    Article  PubMed  Google Scholar 

  25. Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ. Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol. 2008;9:453–61. doi:10.1016/s1470-2045(08)70125-6.

    Article  PubMed  Google Scholar 

  26. Mehta AI, Kanaly CW, Friedman AH, Bigner DD, Sampson JH. Monitoring radiographic brain tumor progression. Toxins (Basel). 2011;3:191–200. doi:10.3390/toxins3030191.

    Article  Google Scholar 

  27. Gerstner ER, Frosch MP, Batchelor TT. Diffusion magnetic resonance imaging detects pathologically confirmed, nonenhancing tumor progression in a patient with recurrent glioblastoma receiving bevacizumab. J Clin Oncol. 2010;28:e91–3. doi:10.1200/JCO.2009.25.0233.

    Article  PubMed  Google Scholar 

  28. Kelly PJ, Weiss SE, Sher DJ, Perez-Atayde AR, Dal Cin P, Choueiri TK. Sunitinib-induced pseudoprogression after whole-brain radiotherapy for metastatic renal cell carcinoma. J Clin Oncol. 2010;28:e433–5. doi:10.1200/JCO.2009.26.8193.

    Article  PubMed  Google Scholar 

  29. Brandsma D, van den Bent MJ. Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol. 2009;22:633–8. doi:10.1097/WCO.0b013e328332363e.

    Article  PubMed  Google Scholar 

  30. Quant EC, Wen PY. Response assessment in neuro-oncology. Curr Oncol Rep. 2011;13:50–6. doi:10.1007/s11912-010-0143-y.

    Article  PubMed  Google Scholar 

  31. 18F ML-10 for early detection of response of brain metastases to WBRT NCT 00791063 [database on the Internet]. National Library of Medicine, Bethesda, MD, USA. 2000. Accessed June 18, 2013.

  32. 18F-FLT-PET Imaging of the brain in patients with metastatic breast cancer to the brain rreated with whole brain radiation therapy with or without sorafenib: comparison with MR imaging of the brain NCT01621906 [database on the Internet]. National Library of Medicine, Bethesda, MD, USA. 2000. Accessed: June 18, 2013.

  33. Whole brain radiotherapy (WBRT) with sorafenib for breast cancer brain metastases (BCBM) NCT01724606 [database on the Internet]. National Library of Medicine, Bethesda, MD, USA. 2000-. Accessed June 18, 2013.

  34. Adamo B, Deal AM, Burrows E, Geradts J, Hamilton E, Blackwell KL, et al. Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases. Breast Cancer Res. 2011;13:R125. doi:10.1186/bcr3071.

    Article  PubMed  CAS  Google Scholar 

  35. A study of everolimus, trastuzumab and vinorelbine in HER2-positive breast cancer brain metastases NCT01305941 [database on the Internet]. National Library of Medicine, Bethesda, MD, USA. 2000. Accessed June 18, 2013.

  36. Phase 1b/2 trial using lapatinib, everolimus and capecitabine for treatment of HER-2 positive breast cancer with CNS metastasis NCT01783756 [database on the Internet]. National Library of Medicine, Bethesda, MD, USA. 2000. Accessed June 18, 2013.

  37. Che C, Yang G, Thiot C, Lacoste MC, Currie JC, Demeule M, et al. New Angiopep-modified doxorubicin (ANG1007) and etoposide (ANG1009) chemotherapeutics with increased brain penetration. J Med Chem. 2010;53:2814–24. doi:10.1021/jm9016637.

    Article  PubMed  CAS  Google Scholar 

  38. Drappatz J, Brenner A, Wong ET, Eichler A, Schiff D, Groves MD, et al. Phase I study of GRN1005 in recurrent malignant glioma. Clin Cancer Res. 2013;19:1567–76. doi:10.1158/1078-0432.CCR-12-2481.

    Article  PubMed  CAS  Google Scholar 

  39. An Open-label, Phase I/IIa, Dose Escalating Study of 2B3-101 in patients with solid tumors and brain metastases or recurrent malignant glioma.NCT01386580 [database on the Internet]. National Library of Medicine, Bethesda, MD, USA. 2000. Accessed June 18, 2013.

  40. Wei KC, Chu PC, Wang HY, Huang CY, Chen PY, Tsai HC, et al. Focused ultrasound-induced blood–brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: a preclinical study. PLoS One. 2013;8:e58995. doi:10.1371/journal.pone.0058995.

    Article  PubMed  CAS  Google Scholar 

  41. Kroll RA, Neuwelt EA. Outwitting the blood–brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery. 1998;42:1083–99. discussion 99–100.

    Article  PubMed  CAS  Google Scholar 

  42. EGFR inhibition using high dose administration of erlotinib weekly for recurrent malignant gliomas with EGFR variant III mutation NCT01257594 [database on the Internet]. National Library of Medicine, Bethesda, MD, USA. 2000. Accessed: June 18, 2013.

  43. Grommes C, Oxnard GR, Kris MG, Miller VA, Pao W, Holodny AI, et al. "Pulsatile" high-dose weekly erlotinib for CNS metastases from EGFR mutant non-small cell lung cancer. NeuroOncol. 2011;13:1364–9. doi:10.1093/neuonc/nor121.

    Google Scholar 

  44. Togashi Y, Masago K, Fukudo M, Tsuchido Y, Okuda C, Kim YH, et al. Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation. Cancer Chemother Pharmacol. 2011;68:1089–92. doi:10.1007/s00280-011-1691-z.

    Article  PubMed  CAS  Google Scholar 

  45. Margolin K. Ipilimumab in a Phase II trial of melanoma patients with brain metastases. Oncoimmunology. 2012;1:1197–9. doi:10.4161/onci.20687.

    Article  PubMed  Google Scholar 

  46. Sutherland S, Ashley S, Miles D, Chan S, Wardley A, Davidson N, et al. Treatment of HER2-positive metastatic breast cancer with lapatinib and capecitabine in the lapatinib expanded access programme, including efficacy in brain metastases—the UK experience. Br J Cancer. 2010;102:995–1002. doi:10.1038/sj.bjc.6605586.

    Article  PubMed  CAS  Google Scholar 

  47. Metro G, Foglietta J, Russillo M, Stocchi L, Vidiri A, Giannarelli D, et al. Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine. Ann Oncol. 2011;22:625–30. doi:10.1093/annonc/mdq434.

    Article  PubMed  CAS  Google Scholar 

  48. Lin NU, Eierman W, Greil R, Campone M, Kaufman B, Steplewski K, 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. doi:10.1007/s11060-011-0629-y.

    Article  PubMed  CAS  Google Scholar 

  49. Rivera E, Meyers C, Groves M, Valero V, Francis D, Arun B, 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. doi:10.1002/cncr.22127.

    Article  PubMed  CAS  Google Scholar 

  50. Trudeau ME, Crump M, Charpentier D, Yelle L, Bordeleau L, Matthews S, 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. doi:10.1093/annonc/mdl056.

    Article  PubMed  CAS  Google Scholar 

  51. Siena S, Crino L, Danova M, Del Prete S, Cascinu S, Salvagni S, 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;21:655–61. doi:10.1093/annonc/mdp343.

    Article  PubMed  CAS  Google Scholar 

  52. Christodoulou C, Bafaloukos D, Kosmidis P, Samantas E, Bamias A, Papakostas 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 

  53. Abrey LE, Olson JD, Raizer JJ, Mack M, Rodavitch A, Boutros DY, et al. A phase II trial of temozolomide for patients with recurrent or progressive brain metastases. J Neurooncol. 2001;53:259–65.

    Article  PubMed  CAS  Google Scholar 

  54. Iwamoto FM, Omuro AM, Raizer JJ, Nolan CP, Hormigo A, Lassman AB, 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. doi:10.1007/s11060-007-9491-3.

    Article  PubMed  CAS  Google Scholar 

  55. Christodoulou C, Bafaloukos D, Linardou H, Aravantinos G, Bamias A, Carina M, 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(1):61–5. doi:10.1007/s11060-004-9176-0.

    Article  PubMed  CAS  Google Scholar 

  56. Caraglia M, Addeo R, Costanzo R, Montella L, Faiola V, Marra M, et al. Phase II study of temozolomide plus pegylated liposomal doxorubicin in the treatment of brain metastases from solid tumours. Cancer Chemother Pharmacol. 2006;57:34–9. doi:10.1007/s00280-005-0001-z.

    Article  PubMed  CAS  Google Scholar 

  57. Oberhoff C, Kieback DG, Wurstlein R, Deertz H, Sehouli J, van Soest C, et al. Topotecan chemotherapy in patients with breast cancer and brain metastases: results of a pilot study. Onkologie. 2001;24:256–60. doi:55088.

    Article  PubMed  CAS  Google Scholar 

  58. Lin NU, Gelman RS, Younger WJ, Sohl J, Freedman RA, Sorensen, et al. Phase II trial of carboplatin (C) and bevacizumab (BEV) in patients (pts) with breast cancer brain metastases (BCBM) (ASCO Annual Meeting abstract). J Clin Oncol. 2013;31(Suppl).

  59. Newton HB, Slivka MA, Volpi C, Bourekas EC, Christoforidis GA, Baujan MA, et al. Intra-arterial carboplatin and intravenous etoposide for the treatment of metastatic brain tumors. J Neurooncol. 2003;61:35–44.

    Article  PubMed  Google Scholar 

  60. Franciosi V, Cocconi G, Michiara M, Di Costanzo F, Fosser V, Tonato 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.

    Article  PubMed  CAS  Google Scholar 

  61. Cocconi G, Lottici R, Bisagni G, Bacchi M, Tonato M, Passalacqua R, et al. Combination therapy with platinum and etoposide of brain metastases from breast carcinoma. Cancer Investig. 1990;8:327–34.

    Article  CAS  Google Scholar 

  62. 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.

    Article  PubMed  CAS  Google Scholar 

  63. Lassman AB, Abrey LE, Shah GD, Panageas KS, Begemann M, Malkin MG, et al. Systemic high-dose intravenous methotrexate for central nervous system metastases. J Neurooncol. 2006;78:255–60. doi:10.1007/s11060-005-9044-6.

    Article  PubMed  CAS  Google Scholar 

  64. Anders CK, Deal AM, Abramson GV, Liu MC, Storniolo AM, Carpenter JT, et al. TBCRC 018: phase II study of iniparib plus chemotherapy to treat triple-negative breast cancer (TNBC) central nervous system (CNS) metastases (mets) (ASCO Annual Meeting abstract). J Clin Oncol. 2013;31(Suppl).

  65. Kumthekar P, Grimm SA, Avram MJ, Kaklamani V, Helenowski I, Rademaker A, et al. Pharmacokinetics and efficacy of pemetrexed in patients with brain or leptomeningeal metastases. J Neurooncol. 2013;112:247–55. doi:10.1007/s11060-013-1055-0.

    Article  PubMed  CAS  Google Scholar 

  66. Murphy C, Nulsen B, Rump M, Brewer C, Patil SM, Lis E, et al. Phase II trial of patupilone in patients (pts) with breast cancer brain metastases (BCBM) progressing or recurring after whole brain radiotherapy (WBXRT). Breast Cancer Symposium Abstract. 2009.

  67. Freedman RA, Bullitt E, Sun L, Gelman R, Harris G, Ligibel JA, et al. A phase II study of sagopilone (ZK 219477; ZK-EPO) in patients with breast cancer and brain metastases. Clin Breast Cancer. 2011;11(6):376–83. doi:10.1016/j.clbc.2011.03.024.

    Article  PubMed  CAS  Google Scholar 

  68. Lin NU, Schwartzberg LS, Kesari S,Yardley DA,Verma S, Anders CK, et al. A 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 (35th Annual CTRC-AACR San Antonio Breast Cancer Symposium Abstract). Cancer Res. 2012;72(Suppl 3).

  69. Jensen CA, Chan MD, McCoy TP, Bourland JD, deGuzman AF, Ellis TL, et al. Cavity-directed radiosurgery as adjuvant therapy after resection of a brain metastasis. J Neurosurg. 2011;114:1585–91. doi:10.3171/2010.11.JNS10939.

    Article  PubMed  Google Scholar 

  70. Minniti G, Esposito V, Clarke E, Scaringi C, Lanzetta G, Salvati M, et al. Multidose stereotactic radiosurgery (9 gy × 3) of the postoperative resection cavity for treatment of large brain metastases. Int J Radiat Oncol Biol Phys. 2013;86:623–9. doi:10.1016/j.ijrobp.2013.03.037.

    Article  PubMed  Google Scholar 

  71. Carpentier A, McNichols RJ, Stafford RJ, Guichard JP, Reizine D, Delaloge S, et al. Laser thermal therapy: real-time MRI-guided and computer-controlled procedures for metastatic brain tumors. Lasers Surg Med. 2011;43:943–50. doi:10.1002/lsm.21138.

    Article  PubMed  Google Scholar 

  72. Aoyama H. Radiation therapy for brain metastases in breast cancer patients. Breast Cancer. 2011;18:244–51. doi:10.1007/s12282-010-0207-8.

    Article  PubMed  Google Scholar 

  73. • Steeg PS, Camphausen KA, Smith QR. Brain metastases as preventive and therapeutic targets. Nat Rev Cancer. 2011;11(5):352–63. doi:10.1038/nrc3053. This review discusses rationale behind the "secondary prophylaxis".

    Article  PubMed  CAS  Google Scholar 

  74. Peereboom DM, Chao ST, Suh JH, Wang D, Mikkelssen T, Brewer CJ, et al., editors. Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery (SRS) in patients with 1–3 newly diagnosed brain metastases. Chicago: The Annual Meeting of American Society of Clinical Oncology; 2012.

    Google Scholar 

  75. Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006;295:2483–91. doi:10.1001/jama.295.21.2483.

    Article  PubMed  CAS  Google Scholar 

  76. Gondi V, Tome WA, Mehta MP. Why avoid the hippocampus? A comprehensive review. Radiother Oncol. 2010;97:370–6. doi:10.1016/j.radonc.2010.09.013.

    Article  PubMed  Google Scholar 

  77. • Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, et al., editors. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiation therapy (WBRT): first report of RTOG 0614, a placebo-controlled, double-blind, randomized trial. Boston: The Annual Meeting of American Society for Radiation Oncology. 2013;15(10):1429–37. This study showed potential for pharmacologic intervention to prevent neurocognitive side effects from WBRT.

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Aki Morikawa has received research support from the Susan G. Komen Foundation and the ASCO Conquer Cancer Foundation Bonadonna Fellowship. Komal Jhaveri has received research support from the Susan G. Komen Foundation. Andrew D. Seidman has served as a consultant for Genentech/Roche and has received payment for lectures including service on speaker’s bureaus from Genentech, Genomic Health, Eisai, and Celgene.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, 300 E 66th Street, New York, NY, 10065, USA

    Aki Morikawa & Andrew D. Seidman

  2. New York University Cancer Institute, New York, NY, 10016, USA

    Komal Jhaveri

Authors
  1. Aki Morikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Komal Jhaveri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew D. Seidman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrew D. Seidman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morikawa, A., Jhaveri, K. & Seidman, A.D. Clinical Trials for Breast Cancer with Brain Metastases: Challenges and New Directions. Curr Breast Cancer Rep 5, 293–301 (2013). https://doi.org/10.1007/s12609-013-0120-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12609-013-0120-1

Keywords

Search

Navigation