Journal of Neuro-Oncology

, Volume 88, Issue 3, pp 359–365

Brain metastases in breast cancer: clinical and pathologic characteristics associated with improvements in survival

  • Michelle E. Melisko
  • Dan H. Moore
  • Penny K. Sneed
  • Julia De Franco
  • Hope S. Rugo
Clinical-patient Studies

Abstract

Background As breast cancer patients live longer with control of systemic disease, survival after the diagnosis of brain metastases (BM) also appears to be improving. Methods The authors conducted a retrospective review of 112 breast cancer patients diagnosed with BM from 1997 to 2007 and correlated clinical and pathologic characteristics including hormone receptor (HR) and Her2/neu status with outcomes. Findings Median time to BM diagnosis (TTBM) was 38 months (range, 0–204 months). TTBM was shorter for patients with HR− versus HR+ disease (median 28.8 vs. 61.2 months, P < 0.001, Wilcoxon test). No difference in TTBM was observed for patients with HER2− versus HER2+ disease (median 37.4 vs. 34.9 months, P = 0.81). Median survival after the diagnosis of BM was 14.4 months. There was no significant difference in median survival after BM diagnosis for patients with HR+ versus HR− cancers (19.9 vs. 11.0 months, P = 0.18, log rank) or for patients with HER2+ versus HER2− disease (23.1 vs. 13.3 months, P = 0.11, log rank). Survival was significantly longer in patients with stable or responding systemic disease at BM diagnosis compared to patients with progressing systemic disease (31 vs. 6.3 months, P < 0.001). Multivariate analysis revealed that HR positivity, age <50, Karnofsky Performance Score (KPS) ≥80, and stable or responding systemic disease at BM diagnosis were associated with improved survival. Interpretation Subsets of patients with breast cancer BM are surviving longer. Control of systemic disease was most strongly associated with improved outcomes, and HER2/neu overexpression did not shorten survival after the diagnosis of BM.

Keywords

Breast carcinoma Brain metastases Leptomeningeal disease Survival Whole brain radiotherapy Stereotactic radiosurgery 

References

  1. 1.
    DiStefano A, Yong Yap Y, Hortobagyi GN, Blumenschein GR (1979) The natural history of breast cancer patients with brain metastases. Cancer 44:1913–1918PubMedCrossRefGoogle Scholar
  2. 2.
    Tsukada Y, Fouad A, Pickren JW, Lane WW (1983) Central nervous system metastasis from breast carcinoma. Autopsy study. Cancer 52:2349–2354PubMedCrossRefGoogle Scholar
  3. 3.
    Lai R, Dang CT, Malkin MG, Abrey LE (2004) The risk of central nervous system metastases after trastuzumab therapy in patients with breast carcinoma. Cancer 101:810–816PubMedCrossRefGoogle Scholar
  4. 4.
    Boogerd W, Vos VW, Hart AA, Baris G (1993) Brain metastases in breast cancer; natural history, prognostic factors and outcome. J Neurooncol 15:165–174PubMedCrossRefGoogle Scholar
  5. 5.
    Sneed PK, Larson DA, Wara WM (1996) Radiotherapy for cerebral metastases. Neurosurg Clin N Am 7:505–515PubMedGoogle Scholar
  6. 6.
    Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, Macdonald JS, Young B (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:494–500PubMedGoogle Scholar
  7. 7.
    Pieper DR, Hess KR, Sawaya RE (1997) Role of surgery in the treatment of brain metastases in patients with breast cancer. Ann Surg Oncol 4:481–490PubMedCrossRefGoogle Scholar
  8. 8.
    Bendell JC, Domchek SM, Burstein HJ, Harris L, Younger J, Kuter I, Bunnell C, Rue M, Gelman R, Winer E (2003) Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97:2972–2977PubMedCrossRefGoogle Scholar
  9. 9.
    Evans AJ, James JJ, Cornford EJ, Chan SY, Burrell HC, Pinder SE, Gutteridge E, Robertson JF, Hornbuckle J, Cheung KL (2004) Brain metastases from breast cancer: identification of a high-risk group. Clin Oncol (R Coll Radiol) 16:345–349Google Scholar
  10. 10.
    Miller KD, Weathers T, Haney LG, Timmerman R, Dickler M, Shen J, Sledge GW Jr (2003) Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival. Ann Oncol 14:1072–1077PubMedCrossRefGoogle Scholar
  11. 11.
    Schellinger PD, Meinck HM, Thron A (1999) Diagnostic accuracy of MRI compared to CCT in patients with brain metastases. J Neurooncol 44:275–281PubMedCrossRefGoogle Scholar
  12. 12.
    Gabos Z, Sinha R, Hanson J, Chauhan N, Hugh J, Mackey JR, Abdulkarim B (2006) Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J Clin Oncol 24:5658–5663PubMedCrossRefGoogle Scholar
  13. 13.
    Slimane K, Andre F, Delaloge S, Dunant A, Perez A, Grenier J, Massard C, Spielmann M (2004) Risk factors for brain relapse in patients with metastatic breast cancer. Ann Oncol 15:1640–1644PubMedCrossRefGoogle Scholar
  14. 14.
    Stewart JF, King RJ, Sexton SA, Millis RR, Rubens RD, Hayward JL (1981) Oestrogen receptors, sites of metastatic disease and survival in recurrent breast cancer. Eur J Cancer 17:449–453PubMedGoogle Scholar
  15. 15.
    Tham YL, Sexton K, Kramer R, Hilsenbeck S, Elledge R (2006) Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 107:696–704PubMedCrossRefGoogle Scholar
  16. 16.
    Lower EE, Drosick DR, Blau R, Brennan L, Danneman W, Hawley DK (2003) Increased rate of brain metastasis with trastuzumab therapy not associated with impaired survival. Clin Breast Cancer 4:114–119PubMedCrossRefGoogle Scholar
  17. 17.
    Kirsch DG, Ledezma CJ, Mathews CS, Bhan AK, Ancukiewicz M, Hochberg FH, Loeffler JS (2005) Survival after brain metastases from breast cancer in the trastuzumab era. J Clin Oncol 23: 2114–2116; author reply 2116–2117Google Scholar
  18. 18.
    Firlik KS, Kondziolka D, Flickinger JC, Lunsford LD (2000) Stereotactic radiosurgery for brain metastases from breast cancer. Ann Surg Oncol 7:333–338PubMedCrossRefGoogle Scholar
  19. 19.
    Petrovich Z, Yu C, Giannotta SL, O’Day S, Apuzzo ML (2002) Survival and pattern of failure in brain metastasis treated with stereotactic gamma knife radiosurgery. J Neurosurg 97:499–506PubMedGoogle Scholar
  20. 20.
    Shaw E, Scott C, Suh J, Kadish S, Stea B, Hackman J, Pearlman A, Murray K, Gaspar L, Mehta M, Curran W, Gerber M (2003) RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database. J Clin Oncol 21:2364–2371PubMedCrossRefGoogle Scholar
  21. 21.
    Mehta MP, Rodrigus P, Terhaard CH, Rao A, Suh J, Roa W, Souhami L, Bezjak A, Leibenhaut M, Komaki R, Schultz C, Timmerman R, Curran W, Smith J, Phan SC, Miller RA, Renschler MF (2003) Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases. J Clin Oncol 21:2529–2536PubMedCrossRefGoogle Scholar
  22. 22.
    Allos Therapeutics Reports Results for Phase 3 Enrich Study of Efaproxyn in Women With Brain Metastases Originating From Breast Cancer. Press Release (http://www.allos.com): Allos Therapeutics, Inc, 2007
  23. 23.
    Lin NU, Winer EP (2007) Brain metastases: the HER2 paradigm. Clin Cancer Res 13:1648–1655PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Michelle E. Melisko
    • 1
  • Dan H. Moore
    • 2
  • Penny K. Sneed
    • 3
  • Julia De Franco
    • 1
  • Hope S. Rugo
    • 1
  1. 1.Department of MedicineUniversity of California, San FranciscoSan FranciscoUSA
  2. 2.Department of Epidemiology and BiostatisticsUniversity of California, San FranciscoSan FranciscoUSA
  3. 3.Department of Radiation OncologyUniversity of California, San FranciscoSan FranciscoUSA

Personalised recommendations