Breast Cancer Research and Treatment

, Volume 123, Issue 1, pp 125–128 | Cite as

Concordant HER2 status between metastatic breast cancer cells in CSF and primary breast cancer tissue

  • In Hae Park
  • Youngmee Kwon
  • Jae Y. Ro
  • Keun Seok Lee
  • Jungsil Ro
Preclinical study

Abstract

It is not known whether the HER2 status of malignant CSF cells coincides with that of the original breast carcinoma cells. We investigated whether CSF cytology specimens were suitable to evaluate HER2 status by fluorescence in situ hybridization (FISH) in patient with leptomeningeal metastasis (LM). Both formalin-fixed paraffin-embedded (FFPE) breast cancer tissue and liquid based CSF cytology specimens were evaluated for HER2 status in 16 patients with LM. We evaluated HER2 gene amplification using FISH on destained CSF cytology slides containing a minimum of 20 malignant cells per slide, and compared these with the HER2 status by immunohistochemistry (IHC) or FISH in FFPE tissues. HER2 was considered positive when the HER2:CEP17 ratio was ≥2.0 or IHC 3+. Of 16 cases, four were HER2 positive and 12 were HER2 negative by FISH analysis in CSF cytology. All CSF-positive cases were HER2 positive by IHC in FFPE tissue. Of 12 HER2 FISH-negative cases in CSF cytology, 10 were HER2 negative (IHC 0 or 1+) and two were IHC 2+ in FFPE tissue. Two IHC 2+ cases had HER2:CEP17 ratios of 1.27 and 2.1, respectively, by FISH in FFPE tissue. As a result, the HER2 status concordance rate between metastatic breast cancer cells in CSF and FFPE primary tissue by IHC and FISH was very high. When CSF cytology specimens were appropriately prepared and had adequate cellularity without dry artifacts, the CSF cytology was suitable to evaluate HER2 status by FISH analysis in patients with LM.

Keywords

Breast cancer Leptomeningeal metastasis CSF cytology HER2 FISH 

References

  1. 1.
    Chamberlain MC (1998) Leptomeningeal metastases: a review of evaluation and treatment. J Neurooncol 37:271–284. doi:10.1023/A:1005976926058 CrossRefPubMedGoogle Scholar
  2. 2.
    Kim DY, Lee KW, Yun T, Park SR, Jung JY, Kim DW et al (2003) Comparison of intrathecal chemotherapy for leptomeningeal carcinomatosis of a solid tumor: methotrexate alone versus methotrexate in combination with cytosine arabinoside and hydrocortisone. Jpn J Clin Oncol 33:608–612CrossRefPubMedGoogle Scholar
  3. 3.
    Grossman SA, Finkelstein DM, Ruckdeschel JC, Trump DL, Moynihan T, Ettinger DS (1993) Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group. J Clin Oncol 11:561–569PubMedGoogle Scholar
  4. 4.
    Rudnicka H, Niwinska A, Murawska M (2007) Breast cancer leptomeningeal metastasis-the role of multimodality treatment. J Neurooncol 84:57–62. doi:10.1007/s11060-007-9340-4 CrossRefPubMedGoogle Scholar
  5. 5.
    Wasserstrom WR, Glass JP, Posner JB (1982) Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 49:759–772CrossRefPubMedGoogle Scholar
  6. 6.
    Colozza M, Minenza E, Gori S, Fenocchio D, Paolucci C, Aristei C et al (2009) Extended survival of a HER-2-positive metastatic breast cancer patient with brain metastases also treated with intrathecal trastuzumab. Cancer Chemother Pharmacol 63:1157–1159. doi:10.1007/s00280-008-0859-7 CrossRefPubMedGoogle Scholar
  7. 7.
    Ferrario C, Davidson A, Bouganim N, Aloyz R, Panasci LC (2009) Intrathecal trastuzumab and thiotepa for leptomeningeal spread of breast cancer. Ann Oncol 20:792–795. doi:10.1093/annonc/mdp019 CrossRefPubMedGoogle Scholar
  8. 8.
    Platini C, Long J, Walter S (2006) Meningeal carcinomatosis from breast cancer treated with intrathecal trastuzumab. Lancet Oncol 7:778–780. doi:10.1016/S1470-2045(06)70864-6 CrossRefPubMedGoogle Scholar
  9. 9.
    Sauter G, Lee J, Bartlett JM, Slamon DJ, Press MF (2009) Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol 27:1322–1333. doi:10.1200/JCO.2007.14.8197 CrossRefGoogle Scholar
  10. 10.
    Lin NU, Bellon JR, Winer EP (2004) CNS metastases in breast cancer. J Clin Oncol 22:3608–3617. doi:10.1200/JCO.2004.01.175 CrossRefPubMedGoogle Scholar
  11. 11.
    Park IH, Ro J, Lee KS, Nam BH, Kwon Y, Shin KH (2009) Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer. Ann Oncol 20:56–62. doi:10.1093/annonc/mdn539 CrossRefPubMedGoogle Scholar
  12. 12.
    Clayton AJ, Danson S, Jolly S, Ryder WD, Burt PA, Stewart AL et al (2004) Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 91:639–643. doi:10.1038/sj.bjc.6601970 PubMedGoogle Scholar
  13. 13.
    Shmueli E, Wigler N, Inbar M (2004) Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment. Eur J Cancer 40:379–382. doi:10.1016/j.ejca.2003.09.018 CrossRefPubMedGoogle Scholar
  14. 14.
    Mir O, Ropert S, Alexandre J, Lemare F, Goldwasser F (2008) High-dose intrathecal trastuzumab for leptomeningeal metastases secondary to HER-2 overexpressing breast cancer. Ann Oncol 19:1978–1980. doi:10.1093/annonc/mdn654 CrossRefPubMedGoogle Scholar
  15. 15.
    Stemmler HJ, Mengele K, Schmitt M, Harbeck N, Laessig D, Herrmann KA et al (2008) Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report. Anticancer Drugs 19:832–836. doi:10.1097/CAD.0b013e32830b58b0 CrossRefPubMedGoogle Scholar
  16. 16.
    Stemmler HJ, Schmitt M, Willems A, Bernhard H, Harbeck N, Heinemann V (2007) Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier. Anticancer Drugs 18:23–28. doi:10.1097/01.cad.0000236313.50833.ee CrossRefPubMedGoogle Scholar
  17. 17.
    Liedtke C, Broglio K, Moulder S, Hsu L, Kau SW, Symmans WF et al (2009) Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Ann Oncol. doi:10.1093/annonc/mdp263. (Epub ahead of print)
  18. 18.
    Broom RJ, Tang PA, Simmons C, Bordeleau L, Mulligan AM, O’Malley FP et al (2009) Changes in estrogen receptor, progesterone receptor and Her-2/neu status with time: discordance rates between primary and metastatic breast cancer. Anticancer Res 29:1557–1562PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • In Hae Park
    • 1
  • Youngmee Kwon
    • 1
  • Jae Y. Ro
    • 2
  • Keun Seok Lee
    • 1
  • Jungsil Ro
    • 1
  1. 1.Center for Breast CancerNational Cancer CenterGoyang-siRepublic of Korea
  2. 2.Weill Medical College of Cornell University, The Methodist HospitalHoustonUSA

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