Skip to main content

Advertisement

Log in

Leptomeningeal disease and breast cancer: the importance of tumor subtype

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Breast cancer (BC) is one of the most common tumors to involve the leptomeninges. We aimed to characterize clinical features and outcomes of patients with LMD based on BC subtypes. We retrospectively reviewed records of 233 patients diagnosed with LMD from BC between 1997 and 2012. Survival was estimated by the Kaplan–Meier method and significant differences in survival were determined by Cox proportional hazards or log-rank tests. Of 190 patients with BC subtype available, 67 (35 %) had hormone receptor positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative BC, 56 (29 %) had HER2+BC, and 67 (35 %) had triple-negative BC (TNBC). Median age at LMD diagnosis was 50 years. Median overall survival (OS) from LMD diagnosis was 4.4 months for HER2+BC (95 % CI 2.8, 6.9), 3.7 months (95 % CI 2.4, 6.0) for HR+/HER2−BC, and 2.2 months (95 % CI 1.5, 3.0) for TNBC (p = 0.0002). Older age was associated with worse outcome (p < 0.0001). Patients with HER2+BC and LMD were more likely to receive systemic therapy (ST) (p = 0.001). Use of intrathecal therapy (IT) (52 %) was similar (p = 0.35). Both IT (p < 0.0001) and ST (p < 0.0001) administration were associated with improved OS. After adjusting for age, IT, extracranial disease, and ST, patients with HER2+BC had better OS compared with HR+/HER2−BC (HR 1.72; 95 %CI 1.07–2.76) and TNBC (HR 3.30; 95 %CI 1.98–5.52). LMD carries a dismal prognosis. Modest survival differences by tumor subtype were seen. Patients with HER2+BC had the best outcome. There is an urgent need to develop effective treatment strategies.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Grossman SA, Krabak MJ (1999) Leptomeningeal carcinomatosis. Cancer Treat Rev 25(2):103–119. doi:10.1053/ctrv.1999.0119

    Article  CAS  PubMed  Google Scholar 

  2. Aparicio A, Chamberlain MC (2002) Neoplastic meningitis. Curr Neurol Neurosci Rep 2(3):225–235

    Article  PubMed  Google Scholar 

  3. Jaeckle KA (2006) Neoplastic meningitis from systemic malignancies: diagnosis, prognosis and treatment. Semin Oncol 33(3):312–323. doi:10.1053/j.seminoncol.2006.04.016

    Article  PubMed  Google Scholar 

  4. Armstrong TS, Gilbert MR (2004) The treatment of neoplastic meningitis. Expert Opin Pharmacother 5(9):1929–1935. doi:10.1517/14656566.5.9.1929

    Article  CAS  PubMed  Google Scholar 

  5. Hoffmann AL, Buhk JH, Strik H (2009) Neoplastic meningitis from breast cancer: feasibility and activity of long-term intrathecal liposomal Ara-C combined with dose-dense temozolomide. Anticancer Res 29(12):5191–5195

    CAS  PubMed  Google Scholar 

  6. Boogerd W, van den Bent MJ, Koehler PJ, Heimans JJ, van der Sande JJ, Aaronson NK, Hart AA, Benraadt J, Vecht ChJ (2004) The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study. Eur J Cancer 40(18):2726–2733. doi:10.1016/j.ejca.2004.08.012

    Article  CAS  PubMed  Google Scholar 

  7. Rudnicka H, Niwinska A, Murawska M (2007) Breast cancer leptomeningeal metastasis–the role of multimodality treatment. J Neurooncol 84(1):57–62. doi:10.1007/s11060-007-9340-4

    Article  PubMed  Google Scholar 

  8. Lin NU (2010) Concordance of HER2 in primary tumor and leptomeningeal metastases: now what? Breast Cancer Res Treat 123(1):129–131. doi:10.1007/s10549-009-0720-7

    Article  PubMed  Google Scholar 

  9. Meriggi F, Zaniboni A (2011) Newer avenues for the treatment of leptomeningeal carcinomatosis. Cent Nerv Syst Agents Med Chem 11(1):38–44

    Article  CAS  PubMed  Google Scholar 

  10. Le Rhun E, Taillibert S, Zairi F, Devos P, Pierret MF, Dubois F, Assaker R, Buisset E, Bonneterre J, Baranzelli MC (2011) Clinicopathological features of breast cancers predict the development of leptomeningeal metastases: a case-control study. J Neurooncol 105(2):309–315. doi:10.1007/s11060-011-0592-7

    Article  PubMed  Google Scholar 

  11. Lee S, Ahn HK, Park YH, do Nam H, Lee JI, Park W, Choi DH, Huh SJ, Park KT, Ahn JS, Im YH (2011) Leptomeningeal metastases from breast cancer: intrinsic subtypes may affect unique clinical manifestations. Breast Cancer Res Treat 129(3):809–817. doi:10.1007/s10549-011-1682-0

    Article  PubMed  Google Scholar 

  12. Torrejon D, Oliveira M, Cortes J, Sanchez-Olle G, Gomez P, Bellet M, Saura C, Peg V, Rovira A, Di Cosimo S (2013) Implication of breast cancer phenotype for patients with leptomeningeal carcinomatosis. Breast 22(1):19–23. doi:10.1016/j.breast.2012.10.009

    Article  PubMed  Google Scholar 

  13. Jang G, Lee SS, Ahn JH, Jung KH, Lee H, Gong G, Kim HH, Ahn SD, Son BH, Ahn SH, Kim SB (2011) Clinical features and course of brain metastases in triple-negative breast cancer: comparison with human epidermal growth factor receptor 2-positive and other type at single institution in Korea. Breast Cancer Res Treat 128(1):171–177. doi:10.1007/s10549-011-1526-y

    Article  CAS  PubMed  Google Scholar 

  14. Lim E, Lin NU (2012) New insights and emerging therapies for breast cancer brain metastases. Oncology 26 (7):652-659, 663

  15. Eichler AF, Kuter I, Ryan P, Schapira L, Younger J, Henson JW (2008) Survival in patients with brain metastases from breast cancer: the importance of HER-2 status. Cancer 112(11):2359–2367. doi:10.1002/cncr.23468

    Article  CAS  PubMed  Google Scholar 

  16. Yap HY, Yap BS, Rasmussen S, Levens ME, Hortobagyi GN, Blumenschein GR (1982) Treatment for meningeal carcinomatosis in breast cancer. Cancer 50(2):219–222

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

Dr. Smith reports grants from Varian Medical systems; outside the submitted work. Dr. Esteva reports fees from Genentech, personal fees from Novartis; outside the submitted work. Otherwise there are no financial disclosures, conflicts of interest, or funding sources for the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sausan Abouharb.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abouharb, S., Ensor, J., Loghin, M.E. et al. Leptomeningeal disease and breast cancer: the importance of tumor subtype. Breast Cancer Res Treat 146, 477–486 (2014). https://doi.org/10.1007/s10549-014-3054-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-014-3054-z

Keywords

Navigation