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Management of brain metastases in breast cancer

Nancy U Lin, MD
Naren Ramakrishna, MD, PhD
Section Editor
Lori J Pierce, MD
Deputy Editor
Sadhna R Vora, MD


Breast cancer is the second most common cancer associated with brain metastases in the United States [1]. As patients with advanced breast cancer live longer, the incidence of brain metastases appears to be increasing. In a subset of women, progression in the central nervous system (CNS) has become the major life-limiting problem.

The risk factors, prognosis, and management of brain metastases in breast cancer are presented here. An overview of the presentation, diagnosis, and management of brain metastases (across tumor types) is discussed separately.

(See "Epidemiology, clinical manifestations, and diagnosis of brain metastases".)

(See "Overview of the treatment of brain metastases".)

(See "Treatment of leptomeningeal metastases (carcinomatous meningitis)".)

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Literature review current through: Oct 2017. | This topic last updated: Sep 26, 2017.
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  1. Barnholtz-Sloan JS, Sloan AE, Davis FG, et al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol 2004; 22:2865.
  2. Arvold ND, Oh KS, Niemierko A, et al. Brain metastases after breast-conserving therapy and systemic therapy: incidence and characteristics by biologic subtype. Breast Cancer Res Treat 2012; 136:153.
  3. Tsukada Y, Fouad A, Pickren JW, Lane WW. Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer 1983; 52:2349.
  4. 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.
  5. Slimane K, Andre F, Delaloge S, et al. Risk factors for brain relapse in patients with metastatic breast cancer. Ann Oncol 2004; 15:1640.
  6. Yerushalmi R, Woods R, Kennecke H, et al. Patterns of relapse in breast cancer: changes over time. Breast Cancer Res Treat 2010; 120:753.
  7. 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; 17:935.
  8. 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.
  9. 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.
  10. Gori S, Rimondini S, De Angelis V, et al. Central nervous system metastases in HER-2 positive metastatic breast cancer patients treated with trastuzumab: incidence, survival, and risk factors. Oncologist 2007; 12:766.
  11. Kirsch DG, Ledezma CJ, Mathews CS, et al. Survival after brain metastases from breast cancer in the trastuzumab era. J Clin Oncol 2005; 23:2114.
  12. Duchnowska R, Szczylik C. Central nervous system metastases in breast cancer patients administered trastuzumab. Cancer Treat Rev 2005; 31:312.
  13. Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin Cancer Res 2007; 13:1648.
  14. 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.
  15. 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.
  16. Stemmler HJ, Heinemann V. Central nervous system metastases in HER-2-overexpressing metastatic breast cancer: a treatment challenge. Oncologist 2008; 13:739.
  17. Kennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol 2010; 28:3271.
  18. Dawood S, Lei X, Litton JK, et al. Incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer. Cancer 2012; 118:4652.
  19. 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; 113:2638.
  20. Yin W, Jiang Y, Shen Z, et al. Trastuzumab in the adjuvant treatment of HER2-positive early breast cancer patients: a meta-analysis of published randomized controlled trials. PLoS One 2011; 6:e21030.
  21. Pestalozzi BC, Holmes E, de Azambuja E, et al. CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01). Lancet Oncol 2013; 14:244.
  22. Ramakrishna N, Temin S, Chandarlapaty S, et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2014; 32:2100.
  23. Brown PD, Ballman KV, Cerhan J, et al. N107C/CEC.3: A phase III trial of post-operative SRS compared with WBRT for resected metastatic brain disease. ASTRO Annual Meeting 2016: LBA-1.
  24. Aoyama H, Shirato H, Tago M, 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.
  25. Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 2009; 10:1037.
  26. Soffietti R, Kocher M, Abacioglu UM, et al. A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results. J Clin Oncol 2013; 31:65.
  27. 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; 29:134.
  28. Tsao MN, Rades D, Wirth A, et al. Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline. Pract Radiat Oncol 2012; 2:210.
  29. 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.
  30. Kelly PJ, Lin NU, Claus EB, et al. Salvage stereotactic radiosurgery for breast cancer brain metastases: outcomes and prognostic factors. Cancer 2012; 118:2014.
  31. Stewart DJ, Dahrouge S. Response of brain metastases from breast cancer to megestrol acetate: a case report. J Neurooncol 1995; 24:299.
  32. Salvati M, Cervoni L, Innocenzi G, Bardella L. Prolonged stabilization of multiple and single brain metastases from breast cancer with tamoxifen. Report of three cases. Tumori 1993; 79:359.
  33. Madhup R, Kirti S, Bhatt ML, et al. Letrozole for brain and scalp metastases from breast cancer--a case report. Breast 2006; 15:440.
  34. Lin NU, Bellon JR, Winer EP. CNS metastases in breast cancer. J Clin Oncol 2004; 22:3608.
  35. Boogerd W, Dalesio O, Bais EM, van der Sande JJ. Response of brain metastases from breast cancer to systemic chemotherapy. Cancer 1992; 69:972.
  36. Rosner D, Nemoto T, Lane WW. Chemotherapy induces regression of brain metastases in breast carcinoma. Cancer 1986; 58:832.
  37. Friedman HS, Evans B, Reardon DA. Phase II trial of temozolomide for patients with progressive brain metastases (abstract #408). Proc Am Soc Clin Oncol 2003; 22:102.
  38. Siena S, Landonio G, Beaietta E. Multicenter phase II study of temozolomide therapy for brain metastasis in patients with malignant melanoma, breast cancer, and non-small cell lung cancer (abstract #407). Proc Am Soc Clin Oncol 2003; 22:407.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. Lin NU, Diéras 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.
  45. Petrelli F, Ghidini M, Lonati V, et al. The efficacy of lapatinib and capecitabine in HER-2 positive breast cancer with brain metastases: A systematic review and pooled analysis. Eur J Cancer 2017; 84:141.
  46. Bartsch R, Berghoff AS, Preusser M. Breast cancer brain metastases responding to primary systemic therapy with T-DM1. J Neurooncol 2014; 116:205.
  47. Jacot W, Pons E, Frenel JS, et al. Efficacy and safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases. Breast Cancer Res Treat 2016; 157:307.
  48. Carlson JA, Nooruddin Z, Rusthoven C, et al. Trastuzumab emtansine and stereotactic radiosurgery: an unexpected increase in clinically significant brain edema. Neuro Oncol 2014; 16:1006.
  49. 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.
  50. Lu YS, Chen TW, Lin CH, et al. Bevacizumab preconditioning followed by Etoposide and Cisplatin is highly effective in treating brain metastases of breast cancer progressing from whole-brain radiotherapy. Clin Cancer Res 2015; 21:1851.
  51. Lin NU, Gelman RS, Younger WJ, et al. Phase II trial of carboplatin (C) and bevacizumab (BEV) in patients (pts) with breast cancer brain metastases (BCBM). 49th Annual American Society of Clinical Oncology Meeting 2013, Chicago, IL. J Clin Oncol 2013; suppl:abstr 513.
  52. Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases http://clinicaltrials.gov/ct2/show/NCT01004172 (Accessed on May 09, 2011).
  53. Gonzalez J, Kumar AJ, Conrad CA, Levin VA. Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys 2007; 67:323.
  54. Wong ET, Huberman M, Lu XQ, Mahadevan A. Bevacizumab reverses cerebral radiation necrosis. J Clin Oncol 2008; 26:5649.
  55. DiStefano A, Yong Yap Y, Hortobagyi GN, Blumenschein GR. The natural history of breast cancer patients with brain metastases. Cancer 1979; 44:1913.
  56. Mahmoud-Ahmed AS, Suh JH, Lee SY, et al. Results of whole brain radiotherapy in patients with brain metastases from breast cancer: a retrospective study. Int J Radiat Oncol Biol Phys 2002; 54:810.
  57. Dawood S, Broglio K, Esteva FJ, et al. Defining prognosis for women with breast cancer and CNS metastases by HER2 status. Ann Oncol 2008; 19:1242.
  58. Melisko ME, Moore DH, Sneed PK, et al. Brain metastases in breast cancer: clinical and pathologic characteristics associated with improvements in survival. J Neurooncol 2008; 88:359.
  59. Tham YL, Sexton K, Kramer R, et al. Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 2006; 107:696.
  60. 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.
  61. Eichler AF, Kuter I, Ryan P, et al. Survival in patients with brain metastases from breast cancer: the importance of HER-2 status. Cancer 2008; 112:2359.
  62. Dawood S, Broglio K, Esteva FJ, et al. Survival among women with triple receptor-negative breast cancer and brain metastases. Ann Oncol 2009; 20:621.
  63. Nam BH, Kim SY, Han HS, et al. Breast cancer subtypes and survival in patients with brain metastases. Breast Cancer Res 2008; 10:R20.
  64. Le Scodan R, Massard C, Mouret-Fourme E, et al. Brain metastases from breast carcinoma: validation of the radiation therapy oncology group recursive partitioning analysis classification and proposition of a new prognostic score. Int J Radiat Oncol Biol Phys 2007; 69:839.
  65. 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; 30:419.
  66. Lee S, Ahn HK, Park YH, et al. Leptomeningeal metastases from breast cancer: intrinsic subtypes may affect unique clinical manifestations. Breast Cancer Res Treat 2011; 129:809.