Skip to main content

Chemoprevention for Brain Metastases

Current Oncology Reports volume 14, pages 63–69 (2012)Cite this article

Abstract

With the advent of effective therapies for systemic disease control, the prevalence of brain metastases (BMs) has been increasing. Relapses in the brain are a major barrier to cure in many patients with lung cancer and other malignancies. Effective agents are needed to prophylactically treat micrometastatic disease in patients at high risk for BMs, thereby reducing the incidence. In this report, we review the pathogenesis of and clinical risk factors for BMs, obstacles to BM treatment, and BM chemoprevention in lung cancer, breast cancer, melanoma, and renal cell carcinoma.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

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

  1. 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(12):2972–9.

    PubMed  Article  Google Scholar 

  2. •• Paget S. The distribution of secondary growth in cancer of the breast. Lancet. 1889;133(3421):571–73. Over a century ago in 1889, the “seed and soil” theory was proposed by Stephen Paget to hypothesize what determined which organ should receive disseminated cancer cells. He was convinced that site of secondary growth was not a matter of chance but was the result of favorable interactions between tumor cells (the seeds) and organ microenvironment (the soil).

    Article  Google Scholar 

  3. •• Fidler IJ, Balasubramanian K, Lin Q, Kim SW, Kim SJ. The brain microenvironment and cancer metastasis. Moll Cells. 2010;30(2):93–8. The authors apply Paget’s “seed and soil” hypothesis to BMs and discuss recent understanding of cerebral neoplastic neovascularization and facilitatory role of astrocytes in the development of BMs, giving hope for new therapeutic approaches to treat this fatal disease.

    Article  CAS  Google Scholar 

  4. Chen AM, Jahan TM, Jablons DM, Garcia J, Larson DA. Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall–cell lung cancer: clinical implications for the subsequent management of the brain. Cancer. 2007;109(8):1668–75.

    PubMed  Article  Google Scholar 

  5. Yamanaka R. Medical management of brain metastases from lung cancer (review). Oncol Rep. 2009;22(6):1269–76.

    PubMed  Article  CAS  Google Scholar 

  6. Huang Z, Brdlik C, Jin P, Shapard HM. A pan-HER approach for cancer therapy: background, current status and future development. Expert Opin Biol Ther. 2009;9(1):97–110.

    PubMed  Article  CAS  Google Scholar 

  7. Yatabe Y, Takahashi T, Mitsudomi T. Epidermal growth factor receptor gene amplification is acquired in association with tumor progression of EGFR-mutated lung cancer. Cancer Res. 2008;68(7):2106–11.

    PubMed  Article  CAS  Google Scholar 

  8. •• Bunn PA Jr, Dziadziusko R, Varella-Garcia M, Franklin WA, Witta SE, Kelly K. Hirsch FR. Biological markers for non-small cell lung cancer patient selection for epidermal growth factor receptor tyrosine kinase inhibitor therapy. Clin Cancer Res. 2006;12(12):3652–56. This article summarizes the results of studies using clinical or biological features to predict benefit from EGFR TKIs.

    PubMed  Article  CAS  Google Scholar 

  9. Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med. 2008;358(11):1160–74.

    PubMed  Article  CAS  Google Scholar 

  10. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EFGR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomized, phase 3 study. Lancet Oncol. 2011;Epub ahead of print.

  11. • Heon S, Yeap BY, Britt GJ, et al. Development of central nervous system metastases in patients with advanced non-small cell lung cancer and somatic EF+GFR mutations treated with gefitinib or erlotinib. Clin Cancer Res. 2010;16(23):5873–82. This article reviews the results of a retrospective analysis to suggest a lower risk of brain relapse in patients with EGFR-mutated NSCLC who were initially treated with gefitinib or erlotinib.

    PubMed  Article  CAS  Google Scholar 

  12. Sun M, Behrens C, Feng L, et al. HER family receptor abnormalities in lung cancer brain metastases and corresponding primary tumors. Clin Cancer Res. 2009;15(15):4829–37.

    PubMed  Article  CAS  Google Scholar 

  13. Grinberg-Rashi H, Ofek E, Perelman M, et al. The expression of the three genes in primary non-small cell lung cancer is associated with metastatic spread to the brain. Clin Cancer Res. 2009;15(5):1755–61.

    PubMed  Article  CAS  Google Scholar 

  14. •• Rodriguez E, Lilenbaum RC. Small cell lung cancer: past, present, and future. Curr Oncol Rep. 2010;12(5):327–34. This article looks at the evolution of SCLC treatment and reviews the standard managements that are currently available, as well as ongoing clinical studies.

    PubMed  Article  Google Scholar 

  15. Musolino A, Ciccolallo L, Panebianco M, et al. Multifactorial central nervous system recurrence susceptibility in patients with HER2-positive breast cancer. Cancer. 2011;117(7):1837–46.

    PubMed  Article  Google Scholar 

  16. Chacon RD, Costanzo MV. Triple-negative breast cancer. Breast Cancer Res. 2010;12 Suppl 2:S3. Epub.

    PubMed  Google Scholar 

  17. • Hennecke H, Yerushalmi R, Woods R, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271–77. This article demonstrates that breast cancer subtypes are associated with distinct pattern of metastatic spread and significant difference in survival post-relapse.

    Article  Google Scholar 

  18. •• Arslan C, Dizdar O, Altundag K. Systemic treatment in breast-cancer patients with brain metastasis. Expert Opin Pharmacother. 2010;11(7):1089–100. This article reviews current experience with systemic therapies in the management of patients with BMs from breast cancer.

    PubMed  Article  CAS  Google Scholar 

  19. 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(6):894–900.

    PubMed  Article  CAS  Google Scholar 

  20. Kuhn J, Robins I, Mehta M, et al. Tumor sequestration of lapatinib (NABTC 04–01). Neurooncology. 2008;10:Abstr ET-05.

    Google Scholar 

  21. Lin NU, Carey LA, Liu MC, et al. Phase II trial of lapatinib for brain metastases in patient swith humen epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2008;26(12):1993–9.

    PubMed  Article  CAS  Google Scholar 

  22. Lin NU, Dierras 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.

    PubMed  Article  CAS  Google Scholar 

  23. Geyer CE, Martin A, Newstat B, et al. Lapatinib (L) plus capecitabine (C) in HER2+ advanced breast cancer (ABC): genomic and updated efficacy data. J Clin Oncol. 2007;25:Abstr 1035.

    Google Scholar 

  24. Boccardo F, Kaufman B, Baselga J, et al. Evaluation of lapatinib (Lap) plus capecitabine (Cap) in patients with brain metastases (BM) from HER2+ breast cancer (BC) enrolled in the Lapatinib Expanded Access Program (LEAP) and French Authorisation Temporaire d’ Utilisation (ATU). J Clin Oncol. 2008;26:Abstr 1094.

    Google Scholar 

  25. Sutherland S, Ashley S, Miles D, 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(6):995–100.

    PubMed  Article  CAS  Google Scholar 

  26. •• 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;Epub ahead of print. This article describes the results of a phase 2 trial assessing the clinical activity of lapatinib and capecitabine combination in patients with BMs from breast cancer. It also expounds past and current experience with the combination in the management of this patient population as well as ongoing research to ascertain the role of lapatinib monotherapy or lapatinib plus capecitabine as chemoprevention against brain relapse from breast cancer.

  27. Eigentler TK, Figl A, Krex D, et al. Number of metastases, serum lactate dehydrogenase level, and type of treatment are prognostic factors in patients with brain metastases of malignant melanoma. Cancer. 2011;117(8):1697–703.

    PubMed  Article  Google Scholar 

  28. Zakrzewski J, Geraghty LN, Rose AE, et al. Clinical variables and primary tumor characteristics predictive of the development of melanoma brain metastases and post-brain metastases survival. Cancer. 2011;117(8):1711–20.

    PubMed  Article  Google Scholar 

  29. Bedikian AY, Wei C, Detry M, et al. Predictive factors for the development of brain metastasis in advanced unresectable metastatic melanoma. Am J Clin Oncol. 2010;Epub ahead of print.

  30. Raizer JJ, Hwu WJ, Panageas KS, et al. Brain and leptomeningeal metastases from cutaneous melanoma :survival outcomes based on clinical features. Neuro Oncol. 2008;10(2):199–207.

    PubMed  Article  Google Scholar 

  31. •• Long GV, Kefford RF, Carr PJA, et al. Phase I/II study of GSK2118436, a selective inhibitor of V600 mutant (MUT) BRAF kinase: evidence of activity in melanoma brain metastases (METS). Ann Oncol. 2008;21(Suppl. 8), Abstr LBA27. This abstract describes the results of a phase 1/2 trial of GSK2118436, which demonstrated the activity of this agent in melanoma BMs.

  32. •• Margolin KA, Di Giacomo AM, Maio M. Brain metastasis in melanoma: clinical activity of CTLA-4 antibody therapy. Semin Oncol. 2008;37(5):468–72. This article reviews the results of a phase 2 trial of ipilimumab, which demonstrated similar clinical activity in melanoma BMs, and ongoing and future trials of combined cytotoxic and immunomodulatory therapy by US and Italian multicenter trial groups.

    Article  Google Scholar 

  33. •• Verma J, Jonasch E, Allen P, Tannir N, Mahajan A. Impact of tyrosine kinase inhibitors on the incidence of brain metastasis in metastatic renal cell carcinoma. Cancer. 2011;Epub ahead of print. This article reviews the results of a large retrospective study which demonstrated that treatment with small-molecule TKIs reduced the incidence of BMs. The study also identified that lung metastasis is a risk factor for BM development.

  34. Gore ME, Hariharan S, Porta C, et al. Sunitinib in metastatic renal cell carcinoma patients with brain metastases. Cancer. 2011;117(3):501–9.

    PubMed  Article  CAS  Google Scholar 

  35. Massard C, Zonierek J, Gross-Goupil M, Fizaki K, Szczylik C, Escudier B. Incidence of brain metastases in renal cell carcinoma treated with sorafenib. Ann Oncol. 2010;21(5):1027–31.

    PubMed  Article  CAS  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Affiliations

  1. Clinical Pharmacy Specialist, Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Van A. Trinh

  2. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 430, Houston, TX, 77030, USA

    Wen-Jen Hwu

Authors
  1. Van A. Trinh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wen-Jen Hwu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wen-Jen Hwu.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Trinh, V.A., Hwu, WJ. Chemoprevention for Brain Metastases. Curr Oncol Rep 14, 63–69 (2012). https://doi.org/10.1007/s11912-011-0200-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-011-0200-1

Keywords

  • Chemoprevention
  • Brain metastases
  • Lung cancer
  • Breast cancer
  • Melanoma
  • Renal cell carcinoma